title: An individualized prognostic signature for gastric cancer patients treated with 5-Fluorouracil-based chemotherapy and distinct multi-omics characteristics of prognostic groups.
abstract: 5-Fluorouracil (5-FU)-based chemotherapy is currently the first-line treatment for gastric cancer. In this study, using gene expression profiles for a panel of cell lines with drug sensitivity data and two cohorts of patients, we extracted a signature consisting of two gene pairs (KCNE2 and API5, KCNE2 and PRPF3) whose within-sample relative expression orderings (REOs) could robustly predict prognoses of gastric cancer patients treated with 5-FU-based chemotherapy. This REOs-based signature was insensitive to experimental batch effects and could be directly applied to samples measured by different laboratories. Taking this unique advantage of the REOs-based signature, we classified gastric cancer samples of The Cancer Genome Atlas (TCGA) into two prognostic groups with distinct transcriptional characteristics, circumventing the usage of confounded TCGA survival data. We further showed that the two prognostic groups displayed distinct copy number, gene mutation and DNA methylation landscapes using the TCGA multi-omics data. The results provided hints for understanding molecular mechanisms determining prognoses of gastric cancer patients treated with 5-FU-based chemotherapy.
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Xiangyu
authors: X
authors: Li
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Hao
authors: H
authors: Cai
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Weicheng
authors: W
authors: Zheng
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Mengsha
authors: M
authors: Tong
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Hongdong
authors: H
authors: Li
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Lu
authors: L
authors: Ao
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Jing
authors: J
authors: Li
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Guini
authors: G
authors: Hong
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Mengyao
authors: M
authors: Li
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Qingzhou
authors: Q
authors: Guan
authors: Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
authors: Sheng
authors: S
authors: Yang
authors: Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, USA.
authors: Da
authors: D
authors: Yang
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Xu
authors: X
authors: Lin
authors: Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors: Zheng
authors: Z
authors: Guo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D059467:Transcriptome
chemical_list: D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-Fluorouracil-based chemotherapy; drug resistance; gastric cancer; gene expression; prognostic signature