title: Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers.
abstract: The expression of a number of genes can influence the response rates to chemotherapy while genes encoding receptor tyrosine kinases (RTKs) determine the response to most targeted cancer therapies currently used in clinics. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS, andTOP2A) and five RTKs (EGFR, ERBB2, PDGFRB, VEGFR1andVEGFR2) in non-small cell lung cancer (NSCLC) and esophagus cancer (EC) and the data are compared to gastric cancer (GC) data reported previously. We demonstrate significant differences in the expression profiles between different cancer types as well as heterogeneity among patients within the same cancer type. In all three cancer types, five chemoresistant genes (TOP2A, STMN1, TYMS, BRCA1andRRM1) are coordinately up-regulated in almost all EC, approximately 90% of NSCLC and one third of GC patients. Most EC and nearly half of GC patients have increased expression of the three RTKs critical to angiogenesis (PDGFR, VEGFR1andVEGFR2), while almost none of the NSCLC patients have elevated expression of angiogenic RTKs. A variable percentage of patients in the three cancer types show upregulation of the EGFR family RTKs,EGFRand/orERBB2. It is of interest to note that approximately 10% of the NSCLC and GC patients are triple-negative for the chemosensitivity genes, angiogenic and EGFR RTK genes. The results suggest significant gene expression differences between different cancer types as well as heterogeneity within each cancer type and therefore different molecules should be targeted for future drug development and clinical trials.
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University Augusta, GA, USA.
authors.forename: Shuchun
authors.initials: S
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: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University Augusta, GA, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University Augusta, GA, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Bai
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University Augusta, GA, USA.
authors.forename: Boying
authors.initials: B
authors.lastname: Dun
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Cao
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Changwen
authors.initials: C
authors.lastname: Jing
authors.affiliation: Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University Augusta, GA, USA.
authors.forename: Jinxiong
authors.initials: J
authors.lastname: She
authors.affiliation: Clinical Oncology Research Center, Jiangsu Cancer Hospital Nanjing, Jiangsu Province, People's Republic of China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Feng
keywords: Co-regulation of gene expression; cancer heterogeneity; chemoresistant genes; drug targets; normalization; reference genes