Genetic Polymorphism of PSCA and Risk of Advanced Precancerous Gastric Lesions in a Chinese Population

Objective： To evaluate the relationship between the genetic polymorphism of prostate stem cell antigen （PSCA） and the risk of advanced precancerous gastric lesions including intestinal metaplasia（IM） and dysplasia（Dys）, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer （GC） in China. Methods： The prevalence of gastric lesions including superficial gastritis（SG）, chronic atrophic gastritis（CAG）, IM and Dys was determined by histopathologic examination. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique. The effects of PSCA genetic variant on the risks of IM and Dys were calculated by unconditional logistic regression. Results： Multivariate analysis revealed subjects carrying PSCA rs2294008 CT/TT genotype were associated with an increased risk of IM （OR=1.38, 95% CI=1.11-1.71） and Dys （OR=1.75, 95% CI=1.36-2.26）, especially for subjects with H.pylori infection （IM： OR=1.34, 95% CI=1.05-1.71; Dys： OR=1.82, 95% CI=1.37-2.42）. Furthermore, H. pylori infection and PSCA rs2294008 CT/TT genotype were observed to jointly elevate the risk of IM （OR=3.32, 95% CI=2.33-4.71） and Dys （OR=4.58, 95% CI=2.99-7.04）. Conclusion： This study suggested that PSCA rs2294008 might have an impact on the risk of IM or Dys among the high risk population of GC.

PSCA is a critical biomarker for predicting the prognosis of KRAS/TP53 mutant pancreatic cancer patients

Background:Partly due to the limited effect of chemotherapy or other therapeutic strategies,which may be due to the insufficient knowledge of the tumor promotion markers and targets,pancreatic cancer(PC)holds the position of one of the most malignant tumors.This study aims to find a diagnosis/therapeutic molecule that can predict the prognosis of PC with different gene background.Methods:The Cancer Genome Atlas(TCGA)pancreatic duct adenocarcinoma(PAAD)–based single nucleotide polymorphisms and gene expression data were used to find the differentially expressed genes(DEGs)between KRAS/TP53 mutant samples and no gene mutation samples.Gene Set Enrichment Analysis(GSEA)-based Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and R-based gene oncology(GO)or immune cell invasion assay were used to explore the above DEGs involved pathways.The single-center PC cohort accompanied with next-generation sequence testing was used to verify the TCGA PAAD–based bioinformatic results.Results:First,we found PC patients who harbored KRAS and/or TP53 gene mutation have poor overall survival.Besides,the enrichment analysis showed that mutant KRAS/TP53 was correlated with PC tumor-promotion–related pathways and immune microenvironment.Next,we detected that prostate stem cell antigen(PSCA)was one of the most differential genes in KRAS/TP53 mutant PC tissues.Indeed,the bioinformatic analysis and our clinical data showed that PSCA was a biomarker of poor prognosis in PC.Conclusion:PSCA is a critical biomarker for predicting the prognosis of KRAS/TP53 mutant PC patients.