BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease mortality.Population-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of th...BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease mortality.Population-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of the method over 39 years have not been assessed.METHODS This was a population-based retrospective study.The data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization,including the number and rate of participants and those requiring esophagogastroduodenoscopies(EGDs),the number and rate of participants diagnosed as having GC,and the positive predictive value of the abnormal findings detected by X-ray and confirmed by EGDs.The number and rate of esophageal cancers were also collected.Further,the cost of detecting one GC was evaluated.RESULTS The number of participants has decreased during the last four decades,from 39925 in 1983 to 12923 in 2021.The rate of those requiring EGDs decreased significantly in recent years(P<0.001).The number of participants diagnosed as having GC has also declined,from 76 to 10 cases.However,the rate of cases diagnosed as GC among the participants remained around 0.1%.The positive predictive value increased significantly in recent years except during 1983-1991.The number and rate of accidentally detected esophageal cancers have risen recently,from 0%in 2008 to 0.02%in 2021,one-fifth of the diagnosis rate of GC.One GC diagnosis costs approximately 4200000 Japanese Yen(30000 United States Dollars)for the X-ray screenings and EGDs.CONCLUSION X-ray GC screening in Hiroshima has been efficient,but one challenge is the cost.Esophageal cancers may also need to be considered because they have gradually increased in recent years.展开更多
AIM: To investigate associations between the IL-17 rs2275913 G>A and rs763780 T>C polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-...AIM: To investigate associations between the IL-17 rs2275913 G>A and rs763780 T>C polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric cancer susceptibility systematically. Relevant articles were identified in the MEDLINE, Science Citation Index, Cochrane Library, Pub Med, EMBASE, CINAHL and Current Contents Index databases. We used version 12.0 STATA statistical software to evaluate the statistical data. Two reviewers abstracted the data independently. Odds ratios(ORs) and 95% confidence intervals(95%CIs) were calculated. RESULTS: Seven independent, case-control studies were chosen for the meta-analysis, which included 3210 gastric cancer patients and 3889 healthy controls. The overall estimation showed a positive association between the IL-17 rs2275913 G>A polymorphism and the occurrence of gastric cancer for five genetic models(all P < 0.05) and similar results were observed for the IL-17 rs763780 T>C variation with four genetic models(all P < 0.05), but not for the dominant model(P > 0.05). Subgroup analysis by country revealed that the rs2275913 G>A and rs763780 T>C polymorphisms may be the main risk factor for gastric cancer in Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly correlated with gastric cancer risk in Asian populations, especially those carrying the rs2275913 G>A and rs763780 T>C polymorphisms.展开更多
AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.METHODS: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical histor...AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.METHODS: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable selfadministered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori(H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution. RESULTS: In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverseassociation between vitamin C intake and gastric cancer risk was observed for the highest(≥ 120.67 mg/d) vs the lowest(< 80.14 mg/d) intake category [OR(95%CI): 0.64(0.46-0.88)], with a significant trend across the three intake categories(P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45(0.32-0.63), 0.50(0.34-0.75), 0.45(0.25-0.81)], strawberries [0.56(0.40-0.78), 0.49(0.32-0.74), 0.52(0.29-0.93)], and bananas [0.40(0.29-0.57), 0.41(0.27-0.62), 0.34(0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively.CONCLUSION: A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.展开更多
AIM: To investigate whether the side population (SP) cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer. METHODS: We analyzed the presence of...AIM: To investigate whether the side population (SP) cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer. METHODS: We analyzed the presence of SP cells indifferent human gastric carcinoma cell lines, and then isolated and identified the SP cells from the KATO Ⅲ human gastric cancer cell line by flow cytometry. The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays. The related genes were determined by reverse transcription polymerase chain reaction. To compare tumorigenic ability, SP and non-side population (NSP) cells from the KATO Ⅲ human gastric cancer cell line were subcutaneously injected into nude mice. RESULTS: SP cells from the total population accounted for 0.57% in KATO Ⅲ, 1.04% in Hs-746T, and 0.02% in AGS (CRL-1739). SP cells could grow clonally and have self-renewal capability in conditioned media. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was different between SP and NSP cells. However, there was no apparent difference between SP and NSP cells when they were injected into nude mice. CONCLUSION: SP cells have some cancer stem celllike characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.展开更多
AIM: To define the age scope of high-risk population for esophageal cancer (EC) in Ci county. METHODS: The results of endoscopic examination of 2 013 subjects, cytological screening of 16 763 persons and records of 9 ...AIM: To define the age scope of high-risk population for esophageal cancer (EC) in Ci county. METHODS: The results of endoscopic examination of 2 013 subjects, cytological screening of 16 763 persons and records of 9 265 patients with EC were analyzed by Ridit methods, the standard age group was 45-49 year group. RESULTS: The average age of patients with moderate esophageal epithelium dysplasia by endoscopic examination was 53.5 years, of severe esophageal epithelium dysplasia, 51.4 years, early EC, 55.6 years. The average age of stage one severe epithelium dysplasia (SEEDⅠ) by cytological screening was 51.2 years, of stage two severe epithelium esophageal dysplasia (SEED Ⅱ) 51.6 years, of advanced EC 61.7 years. In the group of 40-year olds, the value of Ridit by pathological diagnosis was 0.46, 95% CI, 0.45-0.47, that by cytological diagnosis was 0.45, 95% CI, 0.43-0.47. As the age increased at five-year intervals, the value of Ridit increased significantly. CONCLUSION: In Ci county of a high incidence area of EC, the age definition of high-risk population should be above 45 years.展开更多
Helicobacter pylori (H. pylorl) is a Gram-negative bac- terium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a m...Helicobacter pylori (H. pylorl) is a Gram-negative bac- terium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrical, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and pos- sibly result from geographical separation of the bac- terium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different popula- tions of H, pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H, pylori. Further studies are indi- cated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals.展开更多
BACKGROUND Gastric cancer significantly contributes to cancer mortality globally.Gastric intestinal metaplasia(GIM)is a stage in the Correa cascade and a premalignant lesion of gastric cancer.The natural history of GI...BACKGROUND Gastric cancer significantly contributes to cancer mortality globally.Gastric intestinal metaplasia(GIM)is a stage in the Correa cascade and a premalignant lesion of gastric cancer.The natural history of GIM formation and progression over time is not fully understood.Currently,there are no clear guidelines on GIM surveillance or management in the United States.AIM To investigate factors associated with GIM development over time in African American-predominant study population.METHODS This is a retrospective longitudinal study in a single tertiary hospital in Washington DC.We retrieved upper esophagogastroduodenoscopies(EGDs)with gastric biopsies from the pathology department database from January 2015 to December 2020.Patients included in the study had undergone two or more EGDswith gastric biopsy.Patients with no GIM at baseline were followed up until they developed GIM or until the last available EGD.Exclusion criteria consisted of patients age<18,pregnancy,previous diagnosis of gastric cancer,and missing data including pathology results or endoscopy reports.The study population was divided into two groups based on GIM status.Univariate and multivariate Cox regression was used to estimate the hazard induced by patient demographics,EGD findings,and Helicobacter pylori(H.pylori)status on the GIM status.RESULTS Of 2375 patients who had at least 1 EGD with gastric biopsy,579 patients were included in the study.138 patients developed GIM during the study follow-up period of 1087 d on average,compared to 857 d in patients without GIM(P=0.247).The average age of GIM group was 64 years compared to 56 years in the non-GIM group(P<0.001).In the GIM group,adding one year to the age increases the risk for GIM formation by 4%(P<0.001).Over time,African Americans,Hispanic,and other ethnicities/races had an increased risk of GIM compared to Caucasians with a hazard ratio(HR)of 2.12(1.16,3.87),2.79(1.09,7.13),and 3.19(1.5,6.76)respectively.No gender difference was observed between the study populations.Gastritis was associated with an increased risk for GIM development with an HR of 1.62(1.07,2.44).On the other hand,H.pylori infection did not increase the risk for GIM.CONCLUSION An increase in age and non-Caucasian race/ethnicity are associated with an increased risk of GIM formation.The effect of H.pylori on GIM is limited in low prevalence areas.展开更多
AIM: To evaluate the association of glutathione S-trans-ferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South...AIM: To evaluate the association of glutathione S-trans-ferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population. METHODS: We conducted a population-based, large- scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSI-F1 were determined using realtime PCR. RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer. CONCLUSION: GSTM1 and GSCI-1 null genotypes were not associated with increased risk of GC or CRC in Koreans.展开更多
Helicobacter pylori (H. pylori) colonize the gastric mucosa of 50% of the world's population. This infection is closely associated with the development of peptic ulcer disease and gastric cancer. The present study ...Helicobacter pylori (H. pylori) colonize the gastric mucosa of 50% of the world's population. This infection is closely associated with the development of peptic ulcer disease and gastric cancer. The present study was conducted to assess the prevalence of H, pylori infection in Moroccan population and the risk to develop gastric precancerous lesions and gastric cancer. Totally, 298 patients were enrolled, 68 of asymptomatic subjects and 230 of patients with gastric diseases. Histological examination was effected to diagnostic gastric lesions and to detect H. pylori. ELISA was used to determine H. pylori status of patients. The prevalence of H. pylori within asymptomatic and symptomatic subjects was observed higher. A significant relationship was detected between H. pylori infection and the risk of gastric diseases (p-value 〈 0.0001). A meaningful association between chronic gastritis increasing and age was observed (p-value = 0.03). The risk to develop gastric cancer among infected patients was observed elevated with rate of 9%. Our results showed a high prevalence of H. pylori in both asymptomatic and gastric diseases patients. We noticed that chronic gastric infection increases with age. We remarked also that the risk to develop gastric cancer among infected patients was elevated in our population.展开更多
AIM: To investigate the incidence and mortality of gastric cancer (GC) in Zhuanghe region, northeast China and the influencing factors for their changing trends.METHODS: All new cancer cases and deaths registered ...AIM: To investigate the incidence and mortality of gastric cancer (GC) in Zhuanghe region, northeast China and the influencing factors for their changing trends.METHODS: All new cancer cases and deaths registered from 2005 to 2010 in Zhuanghe County were reviewed. The annual GC cases, constituent ratio, crude rates,age-standardized rates, their sex and age distribution and temporal trends were assessed. The method of annual percentage change (APC) was used to estimate the trends of GC.RESULTS: Altogether 2634 new cases of GC and 1722 related deaths were registered, which accounted for 21.04% and 19.13% of all cancer-related incidence and deaths, respectively. The age-standardized incidence rate steadily decreased from 57.48 in 2005 to 44.53 in 2010 per 10^5 males, and from 18.13 to 14.70 per 10s females, resulting in a APC of -5.81% for males and -2.89% for females over the entire period. The magnitude of APC in GC mortality amounted to -11.09% and -15.23%, respectively, as the agestandardized mortality rate steadily decreased from 42.08 in 2005 to 23.71 in 2010 per 10^5 males, and from 23.86 to 10.78 per 10^5 females. Females had a significantly lower incidence (a male/female ratio 2.80, P 〈 0.001) and mortality (a male/female ratio 2.30, P 〈 0.001). In both genders, the peak incidence and mortality occurred in the 80-84 years age group. The age-standardized mortality/incidence ratio also decreased from the peak of 0.73 in 2005 to 0.53 in 2010 for males, and from 1.32 to 0.73 for females.CONCLUSION: Encouraging declines of incidence and mortality of GC were observed in Zhuanghe region between 2005 and 2010, possibly due to the economic development and efficient GC control strategies.展开更多
Gastric cancer stem-like cells(GCSCs) have been identified to possess the ability of self-renewal and tumor initi-ation.However,the mechanisms involved remain largely unknown.Here,we isolated and characterized the G...Gastric cancer stem-like cells(GCSCs) have been identified to possess the ability of self-renewal and tumor initi-ation.However,the mechanisms involved remain largely unknown.Here,we isolated and characterized the GCSCs by side population(SP) sorting procedure and cultured sphere cells(SC) from human gastric cancer cell lines SGC-7901,BGC-823,MGC-803,HGC-27 and MKN-28.The sorting and culture assay revealed that SP cells proliferated in an asymmetric division manner.In addition,SP cells exhibited a higher potential of spheroid colony formation and greater drug resistance than non-SP cells(NSP).Moreover,the SC were found with enhanced capabilities of drug resistance in vitro and tumorigenicity in vivo.Sox2 mRNA and protein was highly and significantly overex-pressed in the SP cells and SC.Importantly,downregulation of Sox2 with siRNA obviously reduced spheroid colony formation and doxorubicin efflux,as well as increased apoptosis rate in sphere cells in vitro and suppressed tumori-genicity in vivo.These results suggest that both SP cells and cultured SC enrich with GCSCs and that Sox2 plays a pivotal role in sustaining stem cell properties and might be a potential target for gastric cancer therapy.展开更多
AIM: To determine whether the positive status of human epidermal growth receptor 2(HER2) can be regarded as an effective prognostic factor for patients with gastric cancer(GC) undergoing R0 resection.METHODS: A total ...AIM: To determine whether the positive status of human epidermal growth receptor 2(HER2) can be regarded as an effective prognostic factor for patients with gastric cancer(GC) undergoing R0 resection.METHODS: A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical(IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-nodemetastasis(TNM) stage, with additional adjustment for potential prognostic factors.RESULTS: Among 1562 patients, 548(positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender(P = 0.004), minority(P < 0.001), tumor location(P = 0.001), pathological grade(P < 0.001), TNM stage(P < 0.001) and adjuvant radiotherapy(74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival(HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival(HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages(Ⅰ and Ⅱ). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION: The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.展开更多
BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still...BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.展开更多
BACKGROUND Approximately half of all new cases of gastric cancer(GC)and related deaths occur in China.More than 80%of patients with GC are diagnosed at an advanced stage,which results in poor prognosis.Although HER2-d...BACKGROUND Approximately half of all new cases of gastric cancer(GC)and related deaths occur in China.More than 80%of patients with GC are diagnosed at an advanced stage,which results in poor prognosis.Although HER2-directed therapy and immune checkpoint inhibitors have been somewhat successful,new drugs are still needed for the treatment of GC.Notably,several gene fusion-targeted drugs have been approved by the United States Food and Drug Administration for solid tumors,including GC,such as larotrectinib for NTRK fusion-positive cancers and zenocutuzumab for NRG1 fusion-positive cancers.However,gene fusions involving targetable genes have not been well characterized in Chinese patients with GC.AIM To identify the profile of fusions involving targetable genes in Chinese patients with GC using clinical specimens and determine the distribution of patients with gene fusion variants among the molecular subtypes of GC.METHODS We retrospectively analyzed gene fusion events in tumor tissue samples from 954 Chinese patients with GC.Clinicopathological characteristics were obtained from their medical records.Genetic alterations,such as single nucleotide variants,indels,amplifications,and gene fusions,were identified using a targeted sequencing panel containing 825 genes.Fusions were validated by fluorescence in situ hybridization(FISH)using break-apart probes.The microsatellite instability(MSI)status was evaluated using MSIsensor from the targeted sequencing panel data.Tumor mutational burden(TMB)was calculated using the total number of nonsynonymous mutations divided by the total genomic targeted region.Chi-square analysis was used to determine the enrichment of gene fusions associated with the molecular subtypes of GC.RESULTS We found that 1.68%(16/954)of patients harbored 20 fusion events involving targetable genes.RARA fusions(n=5)were the most common,followed by FGFR2,BRAF,MET,FGFR3,RET,ALK,EGFR,NTRK2,and NRG1 fusions.Two of the RARA fusions,EML4-ALK(E6:E20)and EGFRSEPTIN14(E7:E10),have been identified in other tumors but not in GC.Surprisingly,18 gene fusion events were previously not reported in any cancer types.Twelve of the eighteen novel gene fusions included complete exons encoding functional domains of targetable genes,such as the tyrosine kinase domain of receptor tyrosine kinases and the DNA-and ligand-binding domains of RARA.Consistent with the results of detection using the targeted sequencing fusion panel,the results of FISH(fluorescence in situ hybridization)confirmed the rearrangement of FGFR2 and BRAF in tumors from patients 04 and 09,respectively.Genetic analysis indicated that the fusion genes were significantly enriched in patients with ERBB2 amplification(P=0.02);however,there were no significant differences between fusion-positive and fusion-negative patients in age,sex,MSI status,and TMB.CONCLUSION We characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68%of patients with GC harbor potential targetable gene fusions,which were enriched in patients with ERBB2 amplification.Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy.展开更多
Advanced digestive tract malignant tumors,represented by advanced colorectal cancer,advanced gastric cancer and advanced esophageal cancer,have insidious onsets and high mortality.Western medicine based on targeted th...Advanced digestive tract malignant tumors,represented by advanced colorectal cancer,advanced gastric cancer and advanced esophageal cancer,have insidious onsets and high mortality.Western medicine based on targeted therapy greatly can improves the benefit and efficacy for patients through population stratification,but its population is limited.Traditional Chinese medicine(TCM)has a long history in treatment of tumors,which is an important part of comprehensive treatment of tumors.Clinical observation has shown that different patients could get different efficacy from TCM treatment.Based on real world registration studies,patients with advanced colorectal cancer,advanced gastric cancer or advanced esophageal cancer who had received TCM treatment were observed and followed,and a TCM dominant population that achieved significant efficacy was screened out to carry out multivariate regression analysis,further explore key factors that affect survival in advanced digestive tract malignant tumors,and establish a prediction model of TCM dominant population.It will provide reference for the follow-up TCM treatment,and provide reference for development of individualized treatment plans,making the TCM treatment for advanced digestive tract malignant tumors more targeted,and helping to improve the benefit rate in TCM.展开更多
Background:Gastric cancer mortality decreased substantially over the last decades in most countries worldwide.This study aimed to assess the most recent national trend of gastric cancer mortality and examine the dispa...Background:Gastric cancer mortality decreased substantially over the last decades in most countries worldwide.This study aimed to assess the most recent national trend of gastric cancer mortality and examine the disparity of gastric cancer mortality between rural and urban areas in China.Methods:The crude mortality data of gastric cancer by sex,age group,and area were obtained from China Health Statistical Yearbooks(2003-2015)covering 10%of Chinese population.The age-standardized rates of mortality(ASRM)of gastric cancer in rural and urban areas were estimated using the 2010 Chinese Census population stratified by age,sex,and area.The trend of mortality of gastric cancer was assessed by using Joinpoint analysis.Results:During the 13-year period,the ASRM was reduced from 31.5/100,000 in 2003 to 20.9/100,000 in 2015 in rural areas and from 18.9/100,000 in 2003 to 14.5/100,000 in 2015 in urban areas.In the male population,the annual percent changes of mortality were−2.2%in urban areas(95%confidence interval[CI]−3.8%to−0.6%;P<0.001)and−3.4%in rural areas(95%CI−5.1%to−1.8%;P<0.001).In the female population,the annual percent changes of mortality were−2.7%in urban areas(95%CI−4.2%to−1.2%;P<0.001)and−4.6%in rural areas(95%CI−5.5%to−3.7%;P<0.001).Conclusions:The declining trend of mortality of gastric cancer was presented from 2003 to 2015 in both rural and urban areas in China.The decrease in gastric cancer mortality is greater in rural areas than in urban areas in China.展开更多
Objective:The aim of this study was to investigate the expression of ABCG2 in human gastric carcinoma and its clinical significance.Methods:Expression of ABCG2 was examined with immunohistochemical technique in the sp...Objective:The aim of this study was to investigate the expression of ABCG2 in human gastric carcinoma and its clinical significance.Methods:Expression of ABCG2 was examined with immunohistochemical technique in the specimens from 45 gastric carcinoma tissues and 30 surrounding normal tissues.The mRNA expression of ABCG2 was measured by RT-PCR and real-time quantitative PCR in 30 cases of gastric carcinoma and normal gastric mucosa, respectively.Results:ABCG2 expression was observed in 28 of 45(62.2%) cases by immunohistochemical analysis.In ABCG2-positive tumors, adjacent non-neoplastic tissue was similarly analyzed, revealed that ABCG2 was up-regulated in gastric carcinoma.ABCG2 expression in poorly differentiated/undifferentiated carcinoma was significantly higher than that in well/moderately-differentiated carcinoma(P < 0.05).The mRNA expression of ABCG2 was significantly higher than that in normal gastric mucosa(P < 0.05).Conclusion:ABCG2 plays an important role in the multi-drug resistance of gastric carcinoma.ABCG2 might be an important factor in the research of gastric cancer stem cell.展开更多
文摘BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease mortality.Population-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of the method over 39 years have not been assessed.METHODS This was a population-based retrospective study.The data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization,including the number and rate of participants and those requiring esophagogastroduodenoscopies(EGDs),the number and rate of participants diagnosed as having GC,and the positive predictive value of the abnormal findings detected by X-ray and confirmed by EGDs.The number and rate of esophageal cancers were also collected.Further,the cost of detecting one GC was evaluated.RESULTS The number of participants has decreased during the last four decades,from 39925 in 1983 to 12923 in 2021.The rate of those requiring EGDs decreased significantly in recent years(P<0.001).The number of participants diagnosed as having GC has also declined,from 76 to 10 cases.However,the rate of cases diagnosed as GC among the participants remained around 0.1%.The positive predictive value increased significantly in recent years except during 1983-1991.The number and rate of accidentally detected esophageal cancers have risen recently,from 0%in 2008 to 0.02%in 2021,one-fifth of the diagnosis rate of GC.One GC diagnosis costs approximately 4200000 Japanese Yen(30000 United States Dollars)for the X-ray screenings and EGDs.CONCLUSION X-ray GC screening in Hiroshima has been efficient,but one challenge is the cost.Esophageal cancers may also need to be considered because they have gradually increased in recent years.
文摘AIM: To investigate associations between the IL-17 rs2275913 G>A and rs763780 T>C polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric cancer susceptibility systematically. Relevant articles were identified in the MEDLINE, Science Citation Index, Cochrane Library, Pub Med, EMBASE, CINAHL and Current Contents Index databases. We used version 12.0 STATA statistical software to evaluate the statistical data. Two reviewers abstracted the data independently. Odds ratios(ORs) and 95% confidence intervals(95%CIs) were calculated. RESULTS: Seven independent, case-control studies were chosen for the meta-analysis, which included 3210 gastric cancer patients and 3889 healthy controls. The overall estimation showed a positive association between the IL-17 rs2275913 G>A polymorphism and the occurrence of gastric cancer for five genetic models(all P < 0.05) and similar results were observed for the IL-17 rs763780 T>C variation with four genetic models(all P < 0.05), but not for the dominant model(P > 0.05). Subgroup analysis by country revealed that the rs2275913 G>A and rs763780 T>C polymorphisms may be the main risk factor for gastric cancer in Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly correlated with gastric cancer risk in Asian populations, especially those carrying the rs2275913 G>A and rs763780 T>C polymorphisms.
文摘AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.METHODS: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable selfadministered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori(H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution. RESULTS: In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverseassociation between vitamin C intake and gastric cancer risk was observed for the highest(≥ 120.67 mg/d) vs the lowest(< 80.14 mg/d) intake category [OR(95%CI): 0.64(0.46-0.88)], with a significant trend across the three intake categories(P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45(0.32-0.63), 0.50(0.34-0.75), 0.45(0.25-0.81)], strawberries [0.56(0.40-0.78), 0.49(0.32-0.74), 0.52(0.29-0.93)], and bananas [0.40(0.29-0.57), 0.41(0.27-0.62), 0.34(0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively.CONCLUSION: A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.
文摘AIM: To investigate whether the side population (SP) cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer. METHODS: We analyzed the presence of SP cells indifferent human gastric carcinoma cell lines, and then isolated and identified the SP cells from the KATO Ⅲ human gastric cancer cell line by flow cytometry. The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays. The related genes were determined by reverse transcription polymerase chain reaction. To compare tumorigenic ability, SP and non-side population (NSP) cells from the KATO Ⅲ human gastric cancer cell line were subcutaneously injected into nude mice. RESULTS: SP cells from the total population accounted for 0.57% in KATO Ⅲ, 1.04% in Hs-746T, and 0.02% in AGS (CRL-1739). SP cells could grow clonally and have self-renewal capability in conditioned media. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was different between SP and NSP cells. However, there was no apparent difference between SP and NSP cells when they were injected into nude mice. CONCLUSION: SP cells have some cancer stem celllike characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.
基金Supported by the National Eighth five-year and tenth five year key Scientific Project, No. 85-914-01-02, 2001BA703B10
文摘AIM: To define the age scope of high-risk population for esophageal cancer (EC) in Ci county. METHODS: The results of endoscopic examination of 2 013 subjects, cytological screening of 16 763 persons and records of 9 265 patients with EC were analyzed by Ridit methods, the standard age group was 45-49 year group. RESULTS: The average age of patients with moderate esophageal epithelium dysplasia by endoscopic examination was 53.5 years, of severe esophageal epithelium dysplasia, 51.4 years, early EC, 55.6 years. The average age of stage one severe epithelium dysplasia (SEEDⅠ) by cytological screening was 51.2 years, of stage two severe epithelium esophageal dysplasia (SEED Ⅱ) 51.6 years, of advanced EC 61.7 years. In the group of 40-year olds, the value of Ridit by pathological diagnosis was 0.46, 95% CI, 0.45-0.47, that by cytological diagnosis was 0.45, 95% CI, 0.43-0.47. As the age increased at five-year intervals, the value of Ridit increased significantly. CONCLUSION: In Ci county of a high incidence area of EC, the age definition of high-risk population should be above 45 years.
文摘Helicobacter pylori (H. pylorl) is a Gram-negative bac- terium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrical, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and pos- sibly result from geographical separation of the bac- terium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different popula- tions of H, pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H, pylori. Further studies are indi- cated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals.
文摘BACKGROUND Gastric cancer significantly contributes to cancer mortality globally.Gastric intestinal metaplasia(GIM)is a stage in the Correa cascade and a premalignant lesion of gastric cancer.The natural history of GIM formation and progression over time is not fully understood.Currently,there are no clear guidelines on GIM surveillance or management in the United States.AIM To investigate factors associated with GIM development over time in African American-predominant study population.METHODS This is a retrospective longitudinal study in a single tertiary hospital in Washington DC.We retrieved upper esophagogastroduodenoscopies(EGDs)with gastric biopsies from the pathology department database from January 2015 to December 2020.Patients included in the study had undergone two or more EGDswith gastric biopsy.Patients with no GIM at baseline were followed up until they developed GIM or until the last available EGD.Exclusion criteria consisted of patients age<18,pregnancy,previous diagnosis of gastric cancer,and missing data including pathology results or endoscopy reports.The study population was divided into two groups based on GIM status.Univariate and multivariate Cox regression was used to estimate the hazard induced by patient demographics,EGD findings,and Helicobacter pylori(H.pylori)status on the GIM status.RESULTS Of 2375 patients who had at least 1 EGD with gastric biopsy,579 patients were included in the study.138 patients developed GIM during the study follow-up period of 1087 d on average,compared to 857 d in patients without GIM(P=0.247).The average age of GIM group was 64 years compared to 56 years in the non-GIM group(P<0.001).In the GIM group,adding one year to the age increases the risk for GIM formation by 4%(P<0.001).Over time,African Americans,Hispanic,and other ethnicities/races had an increased risk of GIM compared to Caucasians with a hazard ratio(HR)of 2.12(1.16,3.87),2.79(1.09,7.13),and 3.19(1.5,6.76)respectively.No gender difference was observed between the study populations.Gastritis was associated with an increased risk for GIM development with an HR of 1.62(1.07,2.44).On the other hand,H.pylori infection did not increase the risk for GIM.CONCLUSION An increase in age and non-Caucasian race/ethnicity are associated with an increased risk of GIM formation.The effect of H.pylori on GIM is limited in low prevalence areas.
文摘AIM: To evaluate the association of glutathione S-trans-ferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population. METHODS: We conducted a population-based, large- scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSI-F1 were determined using realtime PCR. RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer. CONCLUSION: GSTM1 and GSCI-1 null genotypes were not associated with increased risk of GC or CRC in Koreans.
文摘Helicobacter pylori (H. pylori) colonize the gastric mucosa of 50% of the world's population. This infection is closely associated with the development of peptic ulcer disease and gastric cancer. The present study was conducted to assess the prevalence of H, pylori infection in Moroccan population and the risk to develop gastric precancerous lesions and gastric cancer. Totally, 298 patients were enrolled, 68 of asymptomatic subjects and 230 of patients with gastric diseases. Histological examination was effected to diagnostic gastric lesions and to detect H. pylori. ELISA was used to determine H. pylori status of patients. The prevalence of H. pylori within asymptomatic and symptomatic subjects was observed higher. A significant relationship was detected between H. pylori infection and the risk of gastric diseases (p-value 〈 0.0001). A meaningful association between chronic gastritis increasing and age was observed (p-value = 0.03). The risk to develop gastric cancer among infected patients was observed elevated with rate of 9%. Our results showed a high prevalence of H. pylori in both asymptomatic and gastric diseases patients. We noticed that chronic gastric infection increases with age. We remarked also that the risk to develop gastric cancer among infected patients was elevated in our population.
基金Supported by Grants from the Tenth Five-Year Program for National Scientific Key Project of China,No.2004BA703B06-2973 National Basic Research Development Program of China,No.2010CB529304the funds for scientific research fromthe Financial Department of Liaoning Province,China,No.2008-621
文摘AIM: To investigate the incidence and mortality of gastric cancer (GC) in Zhuanghe region, northeast China and the influencing factors for their changing trends.METHODS: All new cancer cases and deaths registered from 2005 to 2010 in Zhuanghe County were reviewed. The annual GC cases, constituent ratio, crude rates,age-standardized rates, their sex and age distribution and temporal trends were assessed. The method of annual percentage change (APC) was used to estimate the trends of GC.RESULTS: Altogether 2634 new cases of GC and 1722 related deaths were registered, which accounted for 21.04% and 19.13% of all cancer-related incidence and deaths, respectively. The age-standardized incidence rate steadily decreased from 57.48 in 2005 to 44.53 in 2010 per 10^5 males, and from 18.13 to 14.70 per 10s females, resulting in a APC of -5.81% for males and -2.89% for females over the entire period. The magnitude of APC in GC mortality amounted to -11.09% and -15.23%, respectively, as the agestandardized mortality rate steadily decreased from 42.08 in 2005 to 23.71 in 2010 per 10^5 males, and from 23.86 to 10.78 per 10^5 females. Females had a significantly lower incidence (a male/female ratio 2.80, P 〈 0.001) and mortality (a male/female ratio 2.30, P 〈 0.001). In both genders, the peak incidence and mortality occurred in the 80-84 years age group. The age-standardized mortality/incidence ratio also decreased from the peak of 0.73 in 2005 to 0.53 in 2010 for males, and from 1.32 to 0.73 for females.CONCLUSION: Encouraging declines of incidence and mortality of GC were observed in Zhuanghe region between 2005 and 2010, possibly due to the economic development and efficient GC control strategies.
基金supported in part by the Foundation of State Key Laboratory of Reproductive Medicine,the project funded by the Priority Academic Program Development(PAPD) of Jiangsu Higher Education Institutionsthe National Natural Science Foundation of China(No. 30930080 and 81161120537)
文摘Gastric cancer stem-like cells(GCSCs) have been identified to possess the ability of self-renewal and tumor initi-ation.However,the mechanisms involved remain largely unknown.Here,we isolated and characterized the GCSCs by side population(SP) sorting procedure and cultured sphere cells(SC) from human gastric cancer cell lines SGC-7901,BGC-823,MGC-803,HGC-27 and MKN-28.The sorting and culture assay revealed that SP cells proliferated in an asymmetric division manner.In addition,SP cells exhibited a higher potential of spheroid colony formation and greater drug resistance than non-SP cells(NSP).Moreover,the SC were found with enhanced capabilities of drug resistance in vitro and tumorigenicity in vivo.Sox2 mRNA and protein was highly and significantly overex-pressed in the SP cells and SC.Importantly,downregulation of Sox2 with siRNA obviously reduced spheroid colony formation and doxorubicin efflux,as well as increased apoptosis rate in sphere cells in vitro and suppressed tumori-genicity in vivo.These results suggest that both SP cells and cultured SC enrich with GCSCs and that Sox2 plays a pivotal role in sustaining stem cell properties and might be a potential target for gastric cancer therapy.
基金Supported by National Natural Science Foundation of ChinaNo.81360318+1 种基金the Application and Basic Research Program of Qinghai Province of ChinaNo.2014-Z-745
文摘AIM: To determine whether the positive status of human epidermal growth receptor 2(HER2) can be regarded as an effective prognostic factor for patients with gastric cancer(GC) undergoing R0 resection.METHODS: A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical(IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-nodemetastasis(TNM) stage, with additional adjustment for potential prognostic factors.RESULTS: Among 1562 patients, 548(positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender(P = 0.004), minority(P < 0.001), tumor location(P = 0.001), pathological grade(P < 0.001), TNM stage(P < 0.001) and adjuvant radiotherapy(74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival(HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival(HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages(Ⅰ and Ⅱ). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION: The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.
基金Supported by the Project of NINGBO Leading Medical Health Discipline,No.2022-B11Ningbo Natural Science Foundation,No.202003N4206Public Welfare Foundation of Ningbo,No.2021S108.
文摘BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.
文摘BACKGROUND Approximately half of all new cases of gastric cancer(GC)and related deaths occur in China.More than 80%of patients with GC are diagnosed at an advanced stage,which results in poor prognosis.Although HER2-directed therapy and immune checkpoint inhibitors have been somewhat successful,new drugs are still needed for the treatment of GC.Notably,several gene fusion-targeted drugs have been approved by the United States Food and Drug Administration for solid tumors,including GC,such as larotrectinib for NTRK fusion-positive cancers and zenocutuzumab for NRG1 fusion-positive cancers.However,gene fusions involving targetable genes have not been well characterized in Chinese patients with GC.AIM To identify the profile of fusions involving targetable genes in Chinese patients with GC using clinical specimens and determine the distribution of patients with gene fusion variants among the molecular subtypes of GC.METHODS We retrospectively analyzed gene fusion events in tumor tissue samples from 954 Chinese patients with GC.Clinicopathological characteristics were obtained from their medical records.Genetic alterations,such as single nucleotide variants,indels,amplifications,and gene fusions,were identified using a targeted sequencing panel containing 825 genes.Fusions were validated by fluorescence in situ hybridization(FISH)using break-apart probes.The microsatellite instability(MSI)status was evaluated using MSIsensor from the targeted sequencing panel data.Tumor mutational burden(TMB)was calculated using the total number of nonsynonymous mutations divided by the total genomic targeted region.Chi-square analysis was used to determine the enrichment of gene fusions associated with the molecular subtypes of GC.RESULTS We found that 1.68%(16/954)of patients harbored 20 fusion events involving targetable genes.RARA fusions(n=5)were the most common,followed by FGFR2,BRAF,MET,FGFR3,RET,ALK,EGFR,NTRK2,and NRG1 fusions.Two of the RARA fusions,EML4-ALK(E6:E20)and EGFRSEPTIN14(E7:E10),have been identified in other tumors but not in GC.Surprisingly,18 gene fusion events were previously not reported in any cancer types.Twelve of the eighteen novel gene fusions included complete exons encoding functional domains of targetable genes,such as the tyrosine kinase domain of receptor tyrosine kinases and the DNA-and ligand-binding domains of RARA.Consistent with the results of detection using the targeted sequencing fusion panel,the results of FISH(fluorescence in situ hybridization)confirmed the rearrangement of FGFR2 and BRAF in tumors from patients 04 and 09,respectively.Genetic analysis indicated that the fusion genes were significantly enriched in patients with ERBB2 amplification(P=0.02);however,there were no significant differences between fusion-positive and fusion-negative patients in age,sex,MSI status,and TMB.CONCLUSION We characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68%of patients with GC harbor potential targetable gene fusions,which were enriched in patients with ERBB2 amplification.Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy.
基金Special Projects of Capital Scientific Research on Health Development(No.2016-1-4171)Projects on"Millions"of Talents for Inheritance and Innovation of Traditional Chinese Medicine of National Administration of Traditional Chinese Medicine(Qihuang Projects)。
文摘Advanced digestive tract malignant tumors,represented by advanced colorectal cancer,advanced gastric cancer and advanced esophageal cancer,have insidious onsets and high mortality.Western medicine based on targeted therapy greatly can improves the benefit and efficacy for patients through population stratification,but its population is limited.Traditional Chinese medicine(TCM)has a long history in treatment of tumors,which is an important part of comprehensive treatment of tumors.Clinical observation has shown that different patients could get different efficacy from TCM treatment.Based on real world registration studies,patients with advanced colorectal cancer,advanced gastric cancer or advanced esophageal cancer who had received TCM treatment were observed and followed,and a TCM dominant population that achieved significant efficacy was screened out to carry out multivariate regression analysis,further explore key factors that affect survival in advanced digestive tract malignant tumors,and establish a prediction model of TCM dominant population.It will provide reference for the follow-up TCM treatment,and provide reference for development of individualized treatment plans,making the TCM treatment for advanced digestive tract malignant tumors more targeted,and helping to improve the benefit rate in TCM.
基金This work was supported in part by National Natural Science Foundation of China (Grant 31870983).
文摘Background:Gastric cancer mortality decreased substantially over the last decades in most countries worldwide.This study aimed to assess the most recent national trend of gastric cancer mortality and examine the disparity of gastric cancer mortality between rural and urban areas in China.Methods:The crude mortality data of gastric cancer by sex,age group,and area were obtained from China Health Statistical Yearbooks(2003-2015)covering 10%of Chinese population.The age-standardized rates of mortality(ASRM)of gastric cancer in rural and urban areas were estimated using the 2010 Chinese Census population stratified by age,sex,and area.The trend of mortality of gastric cancer was assessed by using Joinpoint analysis.Results:During the 13-year period,the ASRM was reduced from 31.5/100,000 in 2003 to 20.9/100,000 in 2015 in rural areas and from 18.9/100,000 in 2003 to 14.5/100,000 in 2015 in urban areas.In the male population,the annual percent changes of mortality were−2.2%in urban areas(95%confidence interval[CI]−3.8%to−0.6%;P<0.001)and−3.4%in rural areas(95%CI−5.1%to−1.8%;P<0.001).In the female population,the annual percent changes of mortality were−2.7%in urban areas(95%CI−4.2%to−1.2%;P<0.001)and−4.6%in rural areas(95%CI−5.5%to−3.7%;P<0.001).Conclusions:The declining trend of mortality of gastric cancer was presented from 2003 to 2015 in both rural and urban areas in China.The decrease in gastric cancer mortality is greater in rural areas than in urban areas in China.
基金Supported by a grant of the National Natural Science Foundation of China (No. 30570522)
文摘Objective:The aim of this study was to investigate the expression of ABCG2 in human gastric carcinoma and its clinical significance.Methods:Expression of ABCG2 was examined with immunohistochemical technique in the specimens from 45 gastric carcinoma tissues and 30 surrounding normal tissues.The mRNA expression of ABCG2 was measured by RT-PCR and real-time quantitative PCR in 30 cases of gastric carcinoma and normal gastric mucosa, respectively.Results:ABCG2 expression was observed in 28 of 45(62.2%) cases by immunohistochemical analysis.In ABCG2-positive tumors, adjacent non-neoplastic tissue was similarly analyzed, revealed that ABCG2 was up-regulated in gastric carcinoma.ABCG2 expression in poorly differentiated/undifferentiated carcinoma was significantly higher than that in well/moderately-differentiated carcinoma(P < 0.05).The mRNA expression of ABCG2 was significantly higher than that in normal gastric mucosa(P < 0.05).Conclusion:ABCG2 plays an important role in the multi-drug resistance of gastric carcinoma.ABCG2 might be an important factor in the research of gastric cancer stem cell.