An individualized prognostic signature for gastric cancer patients treated with 5-Fluorouracil-based chemotherapy and distinct multi-omics characteristics of prognostic groups
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Xiangyu Li1, Hao Cai1, Weicheng Zheng1, Mengsha Tong1, Hongdong Li1, Lu Ao1, Jing Li1, Guini Hong1, Mengyao Li1, Qingzhou Guan1, Sheng Yang2, Da Yang3, Xu Lin1, Zheng Guo1
1Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
2Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, China
3Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, USA
Zheng Guo, e-mail: email@example.com
Xu Lin, e-mail: firstname.lastname@example.org
Da Yang, e-mail: email@example.com
Keywords: gastric cancer, 5-Fluorouracil-based chemotherapy, gene expression, drug resistance, prognostic signature
Received: September 26, 2015 Accepted: January 14, 2016 Published: January 30, 2016
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.
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