西藏及我课题组发现高原地区胃癌高发，年龄较平原提前2～10岁，且易感基因与平原存在不同。研究表明高原低氧环境及基因改变可引起胃粘膜损害并可能与胃癌发病相关。最近，课题组人员进一步通过GWAS发现世居高原人群最显著的SNP差异发生在EPAS1基因。EPAS1是缺氧诱导因子家族成员，低氧能上调其表达，EPAS1在肿瘤的增殖、生长中发挥重要作用。因此，我们推测：高原缺氧可引起胃粘膜损害并与胃癌发病有关，EPAS1低氧通路在其中发挥重要作用。本研究拟在高原和平原地区胃癌和正常人群，以质谱分析高原地区胃癌EPAS1参与低氧通路的表达差异，以胃癌细胞系研究常氧、缺氧环境下EPAS1表达、转录活性及低氧通路的变化，进一步分别过表达及RNAi沉默EPAS1后观测对转录活性、低氧通路及细胞生物学特性的影响，并以裸鼠研究成瘤性，为EPAS1参与高原地区胃癌发病的分子机制提出依据，为高原地区胃癌诊治提供新策略。

Studies from Tibet and our research group shows that gastric cancer incidence at the plateau was high and the young people proportion was higher than the plain, the susceptibility genes were also different from the plain. The hypoxia may cause gastric mucosa damage and it maybe is related to the gastric cancer onset at the plateau. Recently, our research staff found further that the most significantly different SNP of the plateau crowd occurred in the EPAS1 gene through whole genome microarray scanning. EPAS1 belongs to the hypoxia-inducible factor family, and hypoxia can promote up-regulation expression of EPAS1. EPAS1 has a strong promoting effect on tumor growth and proliferation. Therefore, we hypothesized that plateau hypoxia may induce gastric mucosal damage and is related to gastric carcinogenesis, EPAS1 hypoxia pathway plays an important role in it. This study intends to study the plateau and plain gastric cancer patients and normal people, analysis the protein expression differences on hypoxia pathway with EPAS1 involvement at gastric cancer at the plateau by mass spectrometric, research the changes of hypoxia pathway expression and transcriptional activity of EPAS1 in gastric cancer cell lines in normoxic or hypoxic environment. Further observing the related gene and protein expression influences in normoxic or hypoxic environment and the tumorigenicity in nude mice under EPAS1 overexpression or silencing by gene transfection or RNAi in vitro and nude mous. This study will puts forward a experiment basis for the molecular mechanism of EPAS1 participating gastric carcinogenesis at the plateau, and provide new strategies for gastric cancer clinical diagnosis and treatment at the plateau.