Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence

• Published in: PloS one Vol. 11; no. 12; p. e0167455
• Main Author: Alajez, Nehad M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.12.2016; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Apoptosis; Biology and Life Sciences; Cancer; Cancer recurrence; Chemotherapy; Colon - pathology; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Data analysis; Datasets; Disease-Free Survival; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genomes; Hazards; Health aspects; Humans; Identification; Kaplan-Meier Estimate; Kinases; Male; Medical prognosis; Medical research; Medicine and Health Sciences; Metastasis; Middle Aged; Multiple regression models; Neoplasm Metastasis - diagnosis; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Patients; Physiological aspects; Prognosis; Proportional Hazards Models; Prostate; Radiation therapy; Rectum - pathology; Regression analysis; Research and Analysis Methods; Stem cells; Survival; Tumors; Vasoactive intestinal peptide; Saudi Arabia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167455

Colorectal cancer (CRC) is the fourth-ranked cause of cancer-related deaths worldwide. Despite recent advances in CRC management, distant recurrence (DR) remains the major cause of mortality in patients with preoperative chemotherapy and radiotherapy, underscoring a need to precisely identify novel gene signatures for predicting the risk of systemic relapse. Herein, we integrated two independent CRC gene expression datasets: the GSE71222 dataset, including 26 patients who developed DR and 126 patients who did not develop DR, and the GSE21510 dataset, including 23 patients who developed DR and 76 patients who did not develop DR. Our data revealed 37 common upregulated genes (fold change (FC) ≥ 1.5, P < 0.05) and three common downregulated genes (FC ≤ 1.5, P < 0.05) between DR and non-recurrent patients from the two datasets. We subsequently validated the upregulated gene panel in the Cancer Genome Atlas CRC datasets (379 patients), which identified a five-gene signature (S100A2, VIP, HOXC6, DACT1, KIF26B) associated with poor overall survival (OS, log-rank test P-value: 1.19 × 10-4) and poor disease-free survival (DFS, log-rank test P-value: 0.002). In a Cox proportional hazards multiple regression model, the five-gene signature and tumor stage retained their significance as independent prognostic factors for CRC DFS and OS. Therefore, our data identified a novel DR gene expression signature associated with worse prognosis in CRC.