title: Delineation of gastric cancer subtypes by co-regulated expression of receptor tyrosine kinases and chemosensitivity genes.
abstract: Chemotherapy plays a key role in improving disease-free survival and overall survival of gastric cancer (GC); however, response rates are variable and a non-negligible proportion of patients undergo toxic and costly chemotherapeutic regimens without a survival benefit. Several studies have shown the existence of GC subtypes which may predict survival and respond differently to chemotherapy. It is also known that the expression level of chemotherapy-related and target therapy-related genes correlates with response to specific antitumor drugs. Nevertheless, these genes have not been considered jointly to define GC subtypes. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS and TOP2A) and five receptor tyrosine kinases (RTKs) (EGFR, ERBB2, PDGFRB, VEGFR1 and VEGFR2). We demonstrate significant heterogeneity of gene expression among GC patients and identified four GC subtypes using the expression profiles of eight genes in two co-regulation groups: chemosensitivity (BRCA1, STMN1, TYMS and TOP2A) and RTKs (EGFR, PDGFRB, VEGFR1 and VEGFR2). The results are of immediate translational value regarding GC diagnostics and therapeutics, as many of these genes are curently widely used in relevant clinical testing.
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China ; Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University Augusta, GA ; Sino-American Institute of Translational Medicine, Nanjing Tech University Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Li
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Wu
authors.affiliation: Sino-American Institute of Translational Medicine, Nanjing Tech University Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Zhenjiang Jintai Life Technologies Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University Augusta, GA ; Sino-American Institute of Translational Medicine, Nanjing Tech University Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University Augusta, GA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University Augusta, GA.
authors.forename: Shan
authors.initials: S
authors.lastname: Bai
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University Augusta, GA.
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Dun
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University Augusta, GA.
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Tang
keywords: Gastric cancer; chemotherapy; co-regulation; gene expression