Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Prevalence of Precancerous Lesions Based on Digital Cervicography with VIA/VILI among Women Positive for High-Risk Human Papillomavirus Serotypes: A Screening Center-Based Study in Cameroon

Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.

Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China

Objective Gastric precancerous conditions such as atrophic gastritis(AG)and intestinal metaplasia(IM)are considered independent risk factors for gastric cancer(GC).The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development.This study investigated the appropriate monitoring interval for AG/IM patients.Methods Totally,957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study.Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia(HGIN)/GC in AG/IM patients,and to determine an appropriate endoscopic monitoring scheme.Results During follow-up,28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia(LGIN)(0.7%),HGIN(0.9%),and GC(1.3%).Multivariate analysis identified H.pylori infection(P=0.022)and extensive AG/IM lesions(P=0.002)as risk factors for HGIN/GC progression(P=0.025).Conclusion In our study,HGIN/GC was present in 2.2%of AG/IM patients.In AG/IM patients with extensive lesions,a 1–2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study

BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.

Detection of Human Papillomavirus DNA and E6/E7 mRNA from HPV Genotypes 16, 18, 31 and 33 in Histologically Confirmed Cases of Cervical Cancer and Precancerous Lesions in Burkina Faso

Introduction: Cervical cancer, caused by persistent high-risk human papillomavirus (HPV) infection, remains a global public health problem. The cellular transformation and maintenance of the malignant phenotype of these HPVs are attributed to the viral oncoproteins E6 and E7. Objective: This study aims to detect the presence of human papillomavirus DNA and E6/E7 oncoprotein mRNA of HPV genotypes 16, 18, 31 and 33 in cases of cervical cancer and precancerous lesions, histologically confirmed in Burkina Faso. Methods: This descriptive cross-sectional study focused on cases of cervical cancer and high-grade intraepithelial neoplasia (CIN) and was conducted from June to December 2022. One hundred (100) samples of fixed and paraffin-embedded tissues were collected from the pathological anatomy and cytology laboratories of hospitals in the capital of Burkina Faso. High-risk human papillomavirus (HR-HPV) DNA was detected using multiplex real-time PCR, while the presence of E6 and E7 mRNA in cervical cancer and high-grade CIN samples was determined using real-time Reverse Transcriptase-PCR (RT-PCR) with TaqMan probes. Results: The mean age of women diagnosed with cervical cancer and high-grade CIN was 50.81 ± 13.65 years, ranging from 22 to 82 years. Cervical cancer and high-grade CIN were positive for at least one high-risk human papillomavirus (HR-HPV) in 80% of cases. The most prevalent genotypes observed were HPV16, 18, 31, and 33, collectively accounting for 70.08% of cases. Of the 89 samples that tested positive for HR-HPV genotypes 16, 18, 31, and 33, 88 (98.88%;95% CI: [94.58 - 99.94]) were also positive for the presence of mRNA encoding the E6 and E7 oncoproteins of HPV16, 18, 31, and 33. Conclusion: In the presence of HPV DNA, testing for E6 and E7 oncoprotein mRNA could serve as a promising biomarker and valuable tool for improved assessment of the progression to cervical cancer.

Screening for Precancerous Cervical Lesions in Women of Reproductive Age in the Kara Region of Togo in 2022

Introduction: Worldwide, cervical cancer is the 4th most common cancer in women and is a public health problem. The objective of this study was to estimate the prevalence of precancerous cervical lesions and to describe its associated factors among women of reproductive age in the Kara region of Togo. Methods: A cross-sectional study was conducted from March 6 to 14, 2022 in 11 health centers in Kara. Data were collected using a standardized questionnaire and screening for precancerous cervical lesions was performed by visual inspection of the cervix, after application of 5% acetic acid and Lugol’s. Logistic regression analysis was performed to describe factors associated with precancerous lesions. Results: A total of 728 women with a median age of 36, interquartile range [31 - 41] were enrolled. The prevalence of precancerous cervical lesions was 3.9%, 95% confidence interval (95% CI: [2.6 - 5.4]. Factors associated with the presence of precancerous lesions were age at first sexual intercourse ≥ 18 years (adjusted odds ratio (aOR = 3.67;95% CI [1.17 - 18.4]) and being a sex worker (aOR = 8.14;95% CI [1.96 - 27.1]). HIV infection was not associated with the presence of precancerous lesions. Conclusion: The results of this study underscore the importance of intensifying cervical cancer screening efforts in resource-limited countries for better management. These efforts should prioritize vulnerable populations such as female sex workers.

Research of Helicobacter pylori infection in precancerous gastric lesions

INTRODUCTION Helicobacter pylori(Hp)infection has beenconsidered to play significant roles in pathogenesisof peptic ulcer.Additionally Hp is associated withthe development of gastric epithelial hyperplasiaand lymphoid malignancies.The InternationalAgency for Research on Cancer has classified lip asa class Ⅰ carcinogen and a definite cause of gastriccancer in humans.Hp infection first causes chronicactive gastritis and may slowly lead to infection ofwhole stomach.In the late stages of infection,mucosal atrophy and intestinal metaplasia(IM),

A preliminary study on ras protein expression in human esophageal cancer and precancerous lesions

INTRODUCTIONThe esophageal carcinoma is a common malignanttumor in Linzhou City (Linxian) of Henan Provincein northern China.Although the etiology andnatural history of csophageal carcinoma are notclear,a substantial amount of evidence has beenprovided to suggest that the development of humanesophageal squamous cell carcinomas (SCC) is amultistage progressive process.An

Latest developments in precancerous lesions of hepatocellular carcinoma

Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.

Expression and significance of Musashi-1 in gastric cancer and precancerous lesions

AIM:To investigate expression of stem cell marker Musashi-1(Msi-1)in relationship to tumorigenesis and progression of intestinal-type gastric cancer(GC).METHODS:Endoscopic biopsy specimens and surgical specimens were obtained,including 54 cases of intestinal-type GC,41 high-grade intraepithelial neoplasia,57low-grade intraepithelial neoplasia,31 intestinal metaplasia,and 36 normal gastric mucosa.Specimens were fixed in 10%paraformaldehyde,conventionally dehydrated,embedded in paraffin,and sliced in 4-μm-thick serial sections.Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen(PCNA)expression.Correlation analysis was conducted between Msi-1 and PCNA expression.The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically.RESULTS:There were significant differences in Msi-1and PCNA expression in different pathological tissues(χ2=15.37,P<0.01;χ2=115.36,P<0.01).Msi-1and PCNA-positive cells were restricted to the isthmus of normal gastric glands.Expression levels of Msi-1and PCNA in intestinal metaplasia were significantly higher than in normal mucosa(U=392.0,P<0.05;U=40.50,P<0.01),whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia.Msi-1 and PCNA expression in intestinaltype GC was higher than in high-grade intraepithelial neoplasia(U=798.0,P<0.05;U=688.0,P<0.01).There was a significantly positive correlation between Msi-1 and PCNA expression(rs=0.20,P<0.01).Msi-1expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage(χ2=12.62,P<0.01;χ2=11.24,P<0.05),but not with depth of invasion and the presence of distant metastasis.CONCLUSION:Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.

Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats

AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3(STAT3) and vascular endothelial growth factor(VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) in Wistar rats.METHODS: One hundred and twenty Wistar rats were randomly divided into two groups(60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups(20 in each group): C/M15, C/M25 and C/M40(15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/m L MNNG. Stomach tissues were collected at the end of the 15 th, 25 th and 40 th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed. RESULTS:(1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group(2.5 ± 1.0, 2.75 ±0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy(6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different(P > 0.05);(2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy(10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different(P > 0.05); and(3) the expression of VEGF was positively correlated with p-STAT3. CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.

Significance and relationship between Cripto-1 and p-STAT3 expression in gastric cancer and precancerous lesions

AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.

Diagnostic aids for detection of oral precancerous conditions

Oral cancer has a tendency to be detected at late stage which is detrimental to the patients because of its high mortality and morbidity rates. Early detection of oral cancer is therefore important to reduce the burden of this devastating disease. In this review article, the most common oral precancerous lesions are discussed and the importance of early diagnosis is emphasized. In addition, the most common non-invasive oral cancer devices that can aid the general practitioners in early diagnosis are also discussed.

Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions

BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.

Gastric precancerous lesions are associated with gene variants in Helicobacter pylori -susceptible ethnic Malays

AIM: To identify genes associated with gastric pre-cancerous lesions in Helicobacter pylori (H. pylori )susceptible ethnic Malays. METHODS: Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as "cases". Thirtyseven Malay subjects who were H. pylori negative and had no precancerous lesions were included as "controls". Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ2 P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers. RESULTS: Of the 23 H. pylori -positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in "cases" vs "controls" for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively. CONCLUSION: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials.

Effect of transplantation of BMMSCs on pathological change of gastric precancerous lesions of rats

Objective:To build the rat model of gastric precancerous lesions and discuss the effect of transplantation of mesenchymal stem cells(BMMSCs) on the pathological change.Methods:The rat model of gastric precancerous lesions was built using N-methyl-N-nitro-N-nitrosoguanidine.After the intravenous transplantation of BMMSCs,the migration and colonization location was then observed,as well as its effect on the related factors of gastric precancerous lesions,including VEGF,IL-10 and IFN-γ.Results:BMMSCs were mainly colonized in the gastric body and gastric antrum,which could be differentiated into the epithelial and interstitial cells.The expression of VEGF in the transplantation group and non-transplantation group was significantly higher than that in the control group(P<0.05);while the expression of VEGF in the transplantation group was significantly higher than that in the non-transplantation group(t=3.88,P<0.001).The expression of serum IL-10 and IFN- y in the transplantation group and non-transplantation group was significantly higher than that in the control group(P<0.05).while the expression of IL-10 and IFN-γ in the transplantation group was significantly lower than that in the non-transplantation group(t=3.03,P=0.004;t=3.80.P<0.001).Conclusions:BMMSCs can be directionally differentiated into the epithelial and interstitial cells and can also regulate the related growth factors and inflammatory factors to reduce the injury of inflammation,relieve or reverse the process of gastric precancerous lesions.

Protein expression trends of DNMT1 in gastrointestinal diseases:From benign to precancerous lesions to cancer

BACKGROUND In recent years,the incidence of gastrointestinal(GI)cancer in China has increased annually.Early detection and appropriate therapy are considered to be the key to treat GI cancer.DNMT1 takes an active part in the advancement of GI cancer,which will change as the disease progresses.But its expression characteristics in the dynamic variations of GI carcinogenesis are still unclear.AIM To investigate the expression characteristics of DNMT1 in different GI diseases.METHODS We detected the expression of DNMT1 in 650 cases of different GI diseases by immunohistochemistry,including 90 cases of chronic superficial gastritis(CSG),72 cases of atrophic gastritis with intestinal metaplasia(AG/GIM),54 cases of low-grade intraepithelial neoplasia(GLIN),66 cases of high-grade intraepithelial neoplasia(GHIN),71 cases of early gastric cancer(EGC),90 cases of normal intestinal mucosa(NIM),54 cases of intestinal low-grade intraepithelial neoplasia(ILIN),71 cases of intestinal high-grade intraepithelial neoplasia(IHIN),and 82 cases of early colorectal cancer(ECRC).RESULTS In the CSG group,all cases showed weakly positive or negative expression of DNMT1.However,in other four groups(AG/GIM,GLIN,GHIN,and EGC),the positive expression rate gradually increased with the severity of the diseases;the negative or weakly positive cases accounted for 55.56%(40/72),38.89%(21/54),1.52%(1/66),and 1.41%(1/71),respectively.Besides,the moderately positive cases were 44.44%(32/72),57.41%(31/54),80.30%(53/66),and 43.66%(31/71),respectively.The strongly positive cases only existed in the GLIN(3.70%,2/54),GHIN(18.18%,12/66),and EGC(54.93%,39/71)groups.The differences between any two groups were statistically significant(P<0.05).Similarly,in the NIM group,cases with weakly positive expression of DNMT1 were predominant(91.11%,82/90),and the rest were moderately positive cases(8.89%,8/90).In the ILIN,IHIN,and ECRC groups,the rates of cases with weak or negative expression of DNMT1 were 46.30%(25/54),12.68%(9/71),and 4.88%(4/82),respectively;with moderately positive expression were 53.70%(29/54),71.83%(51/71),and 34.15%(28/82),respectively;and with strongly positive expression were 0.00%(0/54),15.49%(11/71),and 60.98%(50/82),respectively.The differences between any two groups were also statistically significant(P<0.05).CONCLUSION The overexpression of DNMT1 protein could effectively predict early GI cancers and severe precancerous lesions,which may have potential clinical application value.

Clinical and experimental study of therapeutic effect of Weixibaonizhuan pills on gastric precancerous lesions

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