Zhang Wentao, Liang Ping, Wang Weihua, Dai Peng, Wang Qin, Yan Wei, Zhao Jinrong, Sun Jianbin, Peng Yong, Cui Daxiang, Yan Zhen
State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Int J Mol Sci. 2015 May 21;16(5):11648-58. doi: 10.3390/ijms160511648.
Gastric adenocarcinoma (GAC) imposes a considerable health burden around the world. Gene variation in prostate stem cell antigen gene (PSCA) has been identified to be associated with GAC risk, while the results showed regional variation. To explore the influence of PSCA gene variation on its expression and GAC risk in the Northwest Chinese population, four single nucleotide polymorphisms (SNPs) of PSCA were genotyped in 476 GAC cases and 481 controls using MassARRAY system. Two SNPs of rs2294008 (C>T) and rs2976392 (G>A) were identified to be associated with GAC risk. rs2294008, rs2976392 and rs10216533 made up two statistically significant haplotypes (Hap-CGG and Hap-TAG). Additionally, PSCA expression was analyzed by quantitative real time PCR, immunohistochemistry and tissue microarray. The results showed that PSCA expression was decreased in GAC tissues compared with adjacent normal tissues. For normal tissues, PSCA expression was higher with Hap-TA than that with Hap-CG. For GAC tissues, the differentiation degree of Hap-TA was higher than that of Hap-CG. The expression distribution of PSCA in multiple human organs showed disparity. These results suggest that PSCA gene variation has a potential effect on its expression and GAC risk in the Northwest Chinese population.
胃腺癌（GAC）在全球范围内造成了相当大的健康负担。前列腺干细胞抗原基因（PSCA）的基因变异已被确定与GAC风险相关，但结果显示存在区域差异。为了探讨PSCA基因变异对中国西北人群其表达及GAC风险的影响，使用MassARRAY系统对476例GAC病例和481例对照进行了PSCA的四个单核苷酸多态性（SNP）基因分型。确定rs2294008（C>T）和rs2976392（G>A）这两个SNP与GAC风险相关。rs2294008、rs2976392和rs10216533构成了两个具有统计学意义的单倍型（单倍型-CGG和单倍型-TAG）。此外，通过定量实时PCR、免疫组织化学和组织芯片分析了PSCA的表达。结果显示，与相邻正常组织相比，GAC组织中PSCA表达降低。对于正常组织，单倍型-TA的PSCA表达高于单倍型-CG。对于GAC组织，单倍型-TA的分化程度高于单倍型-CG。PSCA在多个人体器官中的表达分布存在差异。这些结果表明，PSCA基因变异对中国西北人群其表达及GAC风险具有潜在影响。
