Claudin-6 is down-regulated in gastric cancer and its potential pathway.

Claudins are indispensible in modulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. In order to verify the function of claudin-6 in the development of gastric cancer, we investigated claudin-6 expression in different gastric disease tissues. Moreover, we further explored whether overexpression of claudin-6 altered proliferation, apoptosis, migration, invasiveness, differentiation in BGC-823 cells and the potential mechanism. Immunohistochemistry was performed to detect the in situ expression of claudin-6 in different gastric disease tissues; moreover, cell culture, real-time PCR and western blot were used to evaluate the effect of overexpression of claudin-6 in vitro and the related mechanism. The results of immunohistochemical staining showed that the positivity of claudin-6 was significantly higher in superficial gastritis than that in gastric cancer. Overexpression of claudin-6 induced differentiation of BGC-823 cells by inhibiting the JNK pathway. However, it had no effect on proliferation, apoptosis, migration or invasiveness in vitro. The expression of claudin-6 was decreased in gastric cancer. Overexpression of claudin-6 induced differentiation of gastric cancer cells by inhibiting the JNK pathway.

Five P53 SNPs Involved in Low Rectal Cancer Risk and Prognosis in a Chinese Population.

Although the impact and potential mechanisms of p53 polymorphisms on human malignancies have been intensively studied, analyses for association between p53 polymorphisms and colorectal cancer (CRC) risk were still limited to some common variants. Moreover, the majority of previous studies did not classify the specimens of CRC based on tumor location. This case-control study aimed to evaluate the association of five p53 polymorphisms (rs1042522, rs12947788, rs1625895, rs2909430 and rs12951053) with the risk of low rectal cancer (LRC) and investigate the prognostic significance. A total of 347 cases and 353 controls from a Chinese population were recruited and genotyped using KASP assay. Individuals carrying the variant rs12947788 A allele were observed to associate with an increased risk of LRC. After stratification for clinicopathological parameters, rs12947788 was significantly co-related with the histological type of LRC under a dominant model. Although none of the selected p53 polymorphisms was significantly associated with patient prognosis in total population, significant associations with the overall survival were revealed in the heterozygosis carriers vs. wild type carriers model through subgroup analyses based on clinical characteristics. Moreover, haplotype analyses showed that C-A-G-A-A haplotype was associated with a significantly higher LRC risk as compared to the other haplotypes. In low rectal cancer, P53 protein expression was obviously higher in p53 rs1042522 mutant carriers than in other genotypes. Our study further proves the involvement of p53 polymorphisms in pathogenesis of LRC and may provide potential therapeutic implications.

Efficacy analysis of endoscopic submucosal dissection in gastric adenocarcinoma of fundic gland type: five cases of more than 36 months of follow-up.

BACKGROUND: To explore the feasibility, safety, and effectiveness of endoscopic submucosal dissection (ESD) in the treatment of gastric adenocarcinoma of fundic gland type (GA-FG). METHODS: A retrospective analysis was performed for lesion characteristics, treatment, and follow-up of 5 cases of GA-FG patients treated with ESD in our endoscopy center from Jan 2010 to Dec 2018. RESULTS: Among the 5 patients, there were 2 males and 3 females (M:F =2:3). The average age was 59.8±14.4 years old. Four lesions were located at the fundus, while 1 case was located 1.5 cm below the dentate line. Five cases were all flat-uplifted (0-IIa). The average operation time was 28.6±9.0 min. All 5 patients underwent complete resection, and all of them achieved complete resection. There was no recurrence of the 5 cases for 36-49 months of follow-up. CONCLUSIONS: ESD can be used as a method for the treatment of GA-FG.

Epistatic SNP interaction of ERCC6 with ERCC8 and their joint protein expression contribute to gastric cancer/atrophic gastritis risk.

Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) are two indispensable genes for the initiation of transcription-coupled nucleotide excision repair pathway. This study aimed to evaluate the interactions between single nucleotide polymorphisms of ERCC6 (rs1917799) and ERCC8 (rs158572 and rs158916) in gastric cancer and its precancerous diseases. Besides, protein level analysis were performed to compare ERCC6 and ERCC8 expression in different stages of gastric diseases, and to correlate SNPs jointly with gene expression. Sequenom MassARRAY platform method was used to detect polymorphisms of ERCC6 and ERCC8 in 1916 subjects. In situ ERCC6 and ERCC8 protein expression were detected by immunohistochemistry in 109 chronic superficial gastritis, 109 chronic atrophic gastritis and 109 gastric cancer cases. Our results demonstrated pairwise epistatic interactions between ERCC6 and ERCC8 SNPs that ERCC6 rs1917799-ERCC8 rs158572 combination was associated with decreased risk of chronic atrophic gastritis and increased risk of gastric cancer. ERCC6 rs1917799 also showed a significant interaction with ERCC8 rs158916 to reduce gastric cancer risk. The expressions of ERCC6, ERCC8 and ERCC6-ERCC8 combination have similarities that higher positivity was observed in chronic superficial gastritis compared with chronic atrophic gastritis and gastric cancer. As for the effects of ERCC6 and ERCC8 SNPs on the protein expression, single SNP had no correlation with corresponding gene expression, whereas the ERCC6 rs1917799-ERCC8 rs158572 pair had significant influence on ERCC6 and ERCC6-ERCC8 expression. In conclusion, ERCC6 rs1917799, ERCC8 rs158572 and rs158916 demonstrated pairwise epistatic interactions to associate with chronic atrophic gastritis and gastric cancer risk. The ERCC6 rs1917799-ERCC8 rs158572 pair significantly influence ERCC6 and ERCC6-ERCC8 expression.

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer.

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival.