The Clinical and Molecular Characterization of Gastric Cancer Patients in Qinghai-Tibetan Plateau

Gastric cancer was the fifth most common malignancy and the third deadliest cancer (738,000 deaths in 2018) in the world. The analysis of its molecular characteristics has been complicated by histological and intratumor heterogeneity. Furthermore, the previous studies indicate that the incidence of gastric cancer shows wide geographical variation. As the largest and highest region in China, Qinghai-Tibetan Plateau (QTP) is one of the important global biodiversity hotspots. Here, to better understand the mechanism of gastric cancer and offer the targeted therapeutic strategies specially designed for patients in QTP, we collect tumor and blood samples from 30 primary gastric adenocarcinoma cancer patients at Qinghai Provincial People's Hospital. We discuss the clinical and molecular characteristics for these patients that have been ascribed to the unique features in this place, including high altitude (the average height above sea level is around 4,000 m), multi-ethnic groups, and the specific ways of life or habits (such as eating too much beef and mutton, have alcohol and cigarette problem, et al.). By comparing with the western gastric cancer patients collected from TCGA data portal, some unique characteristics for patients in QTP are suggested. They include high incidence in younger people, most of tumor are located in body, most of SNP are detected in chromosome 7, and the very different molecular atlas in minor ethnic groups and Han Chinese. These characteristics will provide the unprecedented opportunity to increase the efficacy for diagnosis and prognosis of gastric cancer in QTP. Furthermore, to suggest the targeted therapeutics specially designed for these 30 patients, an adapted kernel-based learning model and a compilation of pharmacogenomics data of 462 patient-derived tumor cells (PDCs) that illustrate the diverse genetic and molecular backgrounds of cancer patients, were introduced. In conclusion, our study offers a big opportunity to better understand the mechanism of gastric cancer in QTP and guide the optimal patient-tailored therapy for them.