Streptococcus anginosus in the development and treatment of precancerous lesions of gastric cancer

The microbiota is strongly association with cancer.Studies have shown significant differences in the gastric microbiota between patients with gastric cancer(GC)patients and noncancer patients,suggesting that the microbiota may play a role in the development of GC.Although Helicobacter pylori(H.pylori)infection is widely recognized as a primary risk factor for GC,recent studies based on microbiota sequencing technology have revealed that non-H.pylori microbes also have a significant impact on GC.A recent study discovered that Streptococcus anginosus(S.anginosus)is more prevalent in the gastric mucosa of patients with GC than in that of those without GC.S.anginosus infection can spontaneously induce chronic gastritis,mural cell atrophy,mucoid chemotaxis,and heterotrophic hyperplasia,which promote the development of precancerous lesions of GC(PLGC).S.anginosus also disrupts the gastric barrier function,promotes the proliferation of GC cells,and inhibits apoptosis.However,S.anginosus is underrepresented in the literature.Recent reports suggest that it may cause precancerous lesions,indicating its emerging pathogenicity.Modern novel molecular diagnostic techniques,such as polymerase chain reaction,genetic testing,and Ultrasensitive Chromosomal Aneuploidy Detection,can be used to gastric precancerous lesions via microbial markers.Therefore,we present a concise summary of the relationship between S.anginosus and PLGC.Our aim was to further investigate new methods of preventing and treating PLGC by exploring the pathogenicity of S.anginosus on PLGC.

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.

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.

Identification of plasma proteomic signatures associated with the progression of cardia gastric cancer and precancerous lesions

Objective:Considering that there are no effective biomarkers for the screening of cardia gastric cancer(CGC),we developed a noninvasive diagnostic approach,employing data-independent acquisition(DIA)proteomics to identify candidate protein markers.Methods:Plasma samples were obtained from 40 subjects,10 each for CGC,cardia high-grade dysplasia(CHGD),cardia low-grade dysplasia(CLGD),and healthy controls.Proteomic profiles were obtained through liquid chromatography-mass spectrometry(LC-MS/MS-based DIA proteomics.Candidate plasma proteins were identified by weighted gene co-expression network analysis(WGCNA)combined with machine learning and further validated by the Human Protein Atlas(HPA)database.The area under the receiver operating characteristic curve(AUC)was used to evaluate the performance of the biomarker panel.Results:There was a clear distinction in proteomic features among CGC,CHGD,CLGD,and the healthy controls.According to the WGCNA,we found 42 positively associated and 164 inversely associated proteins related to CGC progression and demonstrated several canonical cancer-associated pathways.Combined with the results from random forests,LASSO regression,and immunohistochemical results from the HPA database,we identified three candidate proteins(GSTP1,CSRP1,and LY6G6F)that could together distinguish CLGD(AUC=0.91),CHGD(AUC=0.99)and CGC(AUC=0.98)from healthy controls with excellent accuracy.Conclusions:The panel of protein biomarkers showed promising diagnostic potential for CGC and precancerous lesions.Further validation and a larger-scale study are warranted to assess its potential clinical applications,suggesting a potential avenue for CGC prevention in the future.

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.

Loss of heterozygosity on 10q23.3 and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions

AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions. METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis, and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining. RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperplasia 13.3% (4/30), early stage gastric cancer 20% (6/30), and advanced stage gastric cancer 33.3% (9/30), None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation. CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.

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.

Risk Factors of Precancerous Gastric Lesions in A Population at High Risk of Gastric Cancer

Objective： In cancer prevention, the targeting of precancerous lesions has been recognized as the most promising method. However, little attention has been paid to the risk factors of precancerous gastric lesions, especially in rural China where there is high prevalence of precancerous gastric lesions. We therefore conducted a cross-sectional study in Liaoning province, China, to investigate the potential risk and protective factors of these precancerous gastric lesions. Methods： A total of 1,179 subjects with high risk of gastric cancer from Zhuanghe County were included in this study. Standard questionnaires were used in collecting epidemiological factors and the data were then analyzed by the unconditional logistic regression model. Results： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects, and the association of smoking or drinking and the precancerous gastric lesions increased in strength with the daily consumption and duration. As the factors such as age, gender, smoking, alcohol were controlled, a multivariable analysis revealed that there was a significant correlation between the deep-fry food intake and the gastric epithelial dysplasia with the odds ratio （OR） of 1.78 [95% confidence interval （CI）： 1.01-3.12]. Garlic eating was shown to confer protection against the development of gastric ulcer （OR=0.55, 95% CI： 0.33-0.92）. Conclusion： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects. Deep-fry food intake might be one of the risk factors for the precancerous gastric lesions and garlic eating was shown to confer protection against the development of gastric ulcer among rural Chinese population.

Abnormal Change of p53 Gene in Gastric and PrecancerousLesions and APC Gene Deletion in Gastric Carcinoma and Near Tissues

p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results showed mutation rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37. 5 % (3/8), 42. 11 % (8/19), 53. 33 (16/30) respectively- There was significant dif-ference among groups of metaplasia, dysplasia, cancer and normal controls. Noexon8 mutation was found in metaplasia and dysplasia, but 4 cases were found to have exon8 mutation in cancer group. It is suggested that exon8 mutation occurs at the late stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course ofprecancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,APC was 47,37 % (9/19), 8. 73% (2/23), 16. 67 % (3/18) respectively. LOH of exon4 had something to do with poor differentiation, lymph node metastasis,depth of invasion- LOH of exon4 may be one of prognostic marker of gastric cancer. We are led to conclude that p53 gene mutation is an early event and perhaps work together with ras oncogene in gastric carcinogenesis

Regulative Effect of Traditional Chinese Medicine on Gene-expression Related to Precancerous Lesion of Gastric Cancer

The gene-expression changes related with precancerous lesion of gastric cancer (PLGC) are surveyed. Not only the regulative effect of traditional Chinese medicine (TCM) on oncogene, antioncogene and anti-apoptosis gene that are related with PLGC is analyzed, but also current research state is presented. It's showed that TCM has effects of therapy and inversion on PLGC. These effects are related with the inhibition to related oncogene expression, the regulation and activation to the deletion of antioncogene, the inhibition to the high-expression of mutant gene-protein about antioncogene, and the regulative function to anti-apoptosis gene.

An experimental research of Weining granule in treating gastric precancerous lesions

Objective： To investigate potential therapeutic effects and mechanism of Weining granule in the treatment of gastric precancerous lesions. Methods： Sixty rats were randomly assigned to a blank group or a model group or to receive retinoic acid or high-, medium- or low- dose of Weining granule. General conditions of the animals were observed before and after treatment. Changes in gastric mucosal pathohistology, telomerase activity, proliferation index （PI） and apoptosis index （AI） were measured. Results： General conditions, including activity and eating, were improved in all Weining-granule-treated groups with the numbers of rats having intestinal metaplasia （IM）, atypical hyperplasia （ATP） or positive telomerase activity being significantly lower than those in the model group （P 〈 0.05 or P 〈 0.01）. Compared with the model group, all doses of Weining granule significantly decreased PI （P 〈 0.01） and increased AI （P 〈 0.05）. Conclusion： Weining granule may provide a therapeutic benefit for the treatment of gastric precancerous lesions by inhibiting telomerase activity and proliferation of gastric cancer cells and by accelerating their apoptosis.

Gastric mucosal precancerous lesions in Helicobacter pyloriinfected pediatric patients in central China:A single-center,retrospective investigation

BACKGROUND Helicobacter pylori(H.pylori)infects about 50%of the world population and is the major cause of chronic gastritis,peptic ulcers,and gastric cancer.Chronic H.pylori infection induces gastric mucosal precancerous lesions mostly in adulthood,and it is debatable whether these pathological conditions can occur in childhood and adolescents as well.Since this is a critical issue to determine if intervention should be offered for this population group,we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H.pylori and gastric cancer.AIM To investigate the relationship of H.pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China.METHODS We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms,and finally enrolled 1015 pediatric patients with H.pylori infection and endoscopic and histological data.H.pylori infection status was determined by rapid urease test and histopathological examination.Both clinical and pathological data were collected and analyzed retrospectively.Occurrence of gastric mucosal precancerous lesions,inflammatory activity and degree of inflammatory cell infiltration between H.pylori-positive and-negative groups were compared.RESULTS Among the 1015 eligible children and adolescents,the overall H.pylori infection rate was 84.14%(854/1015).The infection rate increased with age.The incidence of gastric mucosal precancerous lesions in H.pylori-infected children was 4.33%(37/854),which included atrophic gastritis(17 cases),intestinal metaplasia(11 cases)and dysplasia(9 cases).In H.pylori-negative patients,only 1 atrophic gastritis case[0.62%,(1/161)]was found(P<0.05).Active inflammation in H.pyloriinfected patients was significantly higher than that in non-infected patients,and the H.pyloriinfected group showed more severe lymphocyte and neutrophil granulocyte infiltration(P<0.001).In addition,endoscopy revealed that the most common findings in H.pylori-positive patients were antral nodularity,but in H.pylori-negative patients only superficial gastritis was observed.CONCLUSION In children and adolescents,gastric mucosal precancerous lesions occurred in 4.33%of H.pyloriinfected patients in central China.These cases included atrophic gastritis,intestinal metaplasia,and dysplasia.The data revealed an obvious critical issue requiring future investigation and intervention for this population group.

The Role of Ras Gene Mutation in Gastric Cancer and Precancerous Lesions

Abnormality of ras gene family was studied in a total of 206 cases of gastric cancer and precancerous lesions by PCR-RFLP, PCR-SSCP and DNA sequencing. The results showed that mutation rate of H-ras 12 codon in metaplasia,atypical hyperplasia, early-stage cancer and advanced cancer was 16. 7%, 31. 2 %, 50. 0%, and 32. 2%, respectively. In the groups of superficial gastritis and normal controls, no mutation were detected in codon 12 of ras. Mutations of Hras 61 codon and N-ras 12 codon in various groups were the same as those in normal control. K-ras 12 codon mutation was detected in only 2 cases of gastric cancer by using PCR-SSCP, but it was not detected by DNA sequencing, which may be polymorphism. All H-ras 12 codon mutations were G→T mutation. There were significant difference between the groups of metaplasia, dysplasia, gastric carcinoma and normal control group (P<0.05, P<0.01, P<0.01,respectively). It was concluded that H-ras 12 codon mutation was an early event and may play an important role in gastric carcinogenesis. Although K-ras, N-ras mutation rates are high in colon cancer and leukemia, it seems to bear no relationship with gastric cancer.

Clinicopathological significance and relations of Caspase-3 expression, cell proliferation and apoptosis in gastric cancer and the precancerous lesions

Objective： We investigated the relationship between the expression of Caspase-3, cell proliferation and apoptosis in gastric cancer and their precancerous lesions, to explore the tumorigenesis of the stomach mucosa. Methods： Caspase- 3 expression in 13 normal gastric mucosa, 6 chronic atrophic gastritis （CAG）, 31 intestinal metaplasia （IM）, 114 dysplasia （DYS） and 20 gastric carcinomas were investigated immunohistochemically. Cell proliferation was evaluated with anti-Ki-67 immunostaining and apoptosis was evaluated using DNA fragmentation in situ by TdT-mediated dUTP biotin nick end labeling （TUNEL） method. Results： Caspase-3 mild-moderately positive expression was observed in most of normal superficial epithelia, its positively polar distribution in normal mucosa, CAG, IM, DYS and gastric carcinomas changed as seen in TU- NEL, and so did the positive rate. Caspase-3 protein expression showed significantly positive correlation with the number of apoptotic cells labeled with TUNEL （correlation coefficient r = 0,94; P 〈 0101）. Ki-67 expression showed a negative but not significant correlation trend with Caspase-3 （correlation coefficient r = -0.23; P 〉 0.05）. Conclusion： Caspase-3 protein expression was up-regulated from CAG to IM and mild-moderate atypical dysplasia, but down-regulated in severe dysplasia and gastric carcinoma, indicating that inactivity or reduced expression of Caspase-3 is closely correlated with carcinogenesis of the stomach mucosa.

ANTIGEN MG7 IN GASTRIC CANCER AND GASTRIC PRECANCEROUS LESIONS

Objective: To study the dynamic change and its diagnostic significance of MG7 expression in the process of gastric cancer development. Methods: The expression level of antigen MG7 was determined by immunohistochemistry method in 406 cases of gastric mucosa. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry method in 82 cases. Results: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer were increased gradually (P<0.01). The positive rate of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer were increased on sequence (P<0.01). The positive rate of antigen MG7 expression in type III intestinal metaplasia of gastric mucosa had significant difference, compared with that in type I an II intestinal metaplasia (P<0.05). Conclusion: MG7 antigen had close relationship with gastric cancer. Type III intestinal metaplasia, atrophic gastritis and dysplasia should be followed up in order to improve the early detection of gastric cancer. MG7 antigen had great clinical value in the dynamic follow-up of gastric precursors.

Study on the p53 Protein Expression in Gastric Cancer and Precancerous Lesions by Flow Cytometry

At present, p53 gene and its product p53 protein are the hot spot in the field of cancer research. 50% human malignant tumors are associated with p53 alteration. p53 gene mutation is the most common mutation, which can lead to regulation disturbance of cell proliferation. Gastric cancer is the most common disease in China. Its incidence is the second among various malignant tumors.There were reports about p53 protein expression and gastric cancer progression but few report on p53 protein expression in different stages of precancerous lesions was available. In this study,we analyzed p53 protein expression in gastric cancer and precancerous lesions by flow cytometry to evaluate the role of p53 protein in the pathogenesis of gastric cancer.

Review on the progress of treating gastric precancerous lesions with traditional Chinese medicine based on regulatory genes

In recent years,the incidence of Precancerous lesions of gastric cancer(PLGC)has gradually increased,and it is difficult to be cured and easy to recur.Traditional Chinese Medicine(TCM)emphasizes the prevention before the disease.The regulation of PLGC related tumor genes by Chinese medicine has become a research hotspot.This paper summarized PLGC related proto-oncogenes,tumor suppressor genes and apoptosis related genes,and discussed the mechanism of Chinese Medicine Therapy PLGC from the perspective of gene expression,providing new ideas and methods for clinical treatment of PLGC.

Identification of key pathways and genes from gastric precancerous lesions to gastric cancer by integrated bioinformatics analysis

Objective:This work aimed to illuminate the potential key genes and pathways in GC tumorigenesis based on bioinfOrmatics analysis.Methods:The differentially expressed genes(DEGs)between GPL tissue samples and GC tissue samples were investigated using the GSE55696 and GSE87666 microarray data from the Gene Expression Omnibus(GEO)database.DEGs were identified by an empirical Bayes method based on the Limma R package.Then,KEGG and GO enrichment analyses of DEGs were performed followed by protein-protein interaction(PPI)network construction.Finally,the overall survival(OS)analysis of key genes was performed by the Kaplan-Meier plotter online tool.Results:A total of 250 DEGs were obtained,of which 216 were up-regulated and 34 were down-regulated.KEGG pathways analysis showed that the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction,chemokine signaling pathway,metabolic pathways,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,and other signaling pathways about cancer,while no down-regulated pathways were enriched.A PPI network of DEGs was constructed with 117 nodes and 660 edges,and 20 genes were selected as hub genes owing to high degrees in the network.According to the Kaplan-Meier analysis,6 out of 20 hub genes including CCR7,FPR1,C3,CXCR5,GNB4,and PPBP with high mRNA expression were associated with poor OS for GC patients.Conclusion:The results of this study provide possible factors for the occurrence of GC,and the identification of the genes and pathways associated with the progression from GPL to GC provides valuable data for investigating the pathogenesis in future studies.

Comparison between peroral traction-assisted ESD and traditional ESD treatment for early gastric cancer and precancerous lesions

Objective:To explore the differences in the effect of peroral traction-assisted endoscopic submucosal dissection (ESD) and traditional ESD for the treatment of early gastric cancer and precancerous lesions. Methods:112 patients with early gastric cancer and precancerous lesions treated in our hospital between May 2013 and May 2016 were collected and divided into control group and observation group according to the random number table (n=56). Observation group of patients received peroral traction-assisted ESD, and the control group of patients only received traditional ESD. The intraoperative dissected lesion diameter, mean operation time and intraoperative blood loss of two groups of patients were recorded, enzyme-linked immunosorbent assay was used to detect serum inflammatory factor levels, and RIA was used to detect serum stress hormone levels. Results:Dissected lesion diameter of observation group was greater than that of control group (P<0.05) while mean operation time and intraoperative blood loss were less than those of control group (P<0.05);1 d after operation, serum inflammatory factors interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12) and tumor necrosis factor-α(TNF-α) levels of observation group were lower than those of control group (P<0.05), and serum stress hormones cortisol (Cor),β-endorphin (β-EP), epinephrine (E), norepinephrine (NE) and angiotensin II (ATII) levels were lower than those of control group (P<0.05). Conclusions:Peroral traction-assisted ESD can effectively increase the lesion dissection effect and reduce the postoperative inflammatory response and stress response in patients with early gastric cancer and 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.