Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma

// Gang Liu 1, * , Chuanpeng Dong 1, * , Xing Wang 1, * , Guojun Hou 2, * , Yu Zheng 1 , Huilin Xu 1 , Xiaohui Zhan 3 and Lei Liu 1 1 Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China 2 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 3 CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China * These authors have contributed equally to this work Correspondence to: Lei Liu, email: liulei_sibs@163.com Keywords: colorectal cancer; prognosis; transcription factor; model Received: May 07, 2017     Accepted: August 26, 2017     Published: September 28, 2017 ABSTRACT Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.