Cancer Management and Research (Aug 2018)
Computational analysis of mRNA expression profiles identifies a novel triple-biomarker model as prognostic predictor of stage II and III colorectal adenocarcinoma patients
Abstract
Xiankui Cheng,1 Meilin Hu,2 Chuancui Chen,3 Dongsheng Hou1 1Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Endodontics, Tianjin Medical University School of Stomatology, Heping, Tianjin, People’s Republic of China; 3Infectious Diseases Clinic, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Introduction: Although remarkable progress has been made to determine the prognosis of patients with colorectal cancer (CRC), it is inadequate to identify the subset of high-risk TNM stage II and stage III patients that have a high potential of developing tumor recurrence and may experience death. In this study, we aimed to develop biomarkers as a prognostic signature for the clinical outcome of CRC patients with stage II and stage III. Materials and methods: We performed a systematic and comprehensive discovery step to identify recurrence-associated genes in CRC patients through publicly available GSE41258 (n=253) and GSE17536 (n=107) datasets. We subsequently determined the prognostic relevance of candidate genes in stage II and III patients and developed a triple-biomarker for predicting RFS in GSE17536, which was later validated in an independent cohort GSE33113 dataset (n=90). Results: Based upon mRNA expression profiling studies, we identified 45 genes which differentially expressed in recurrent vs non-recurrent CRC patients. By using Cox proportional hazard models, we then developed a triple-marker model (THBS2, SERPINE1, and FN1) to predict prognosis in GSE17536, which successfully identified poor prognosis in stage II and stage III, particularly high-risk stage II CRC patients. Discussion: Notably, we found that our triple-marker model once again predicted recurrence in stage II patients in GSE33113. Kaplan–Meier survival analysis demonstrated that patients with high scores have a poor outcome compared to those with low scores. Our triple-marker model is a reliable predictive tool for determining prognosis in CRC patients with stage II and stage III, and might be able to identify high-risk patients that are candidates for more targeted personalized clinical management and surveillance. Keywords: colorectal cancer, triple-biomarker model, metastasis, retrospective study
