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.
Highlights
Colorectal carcinoma (CRC) is one of the most important causes of death worldwide [1]
We evaluated the activities of regulatory factors, and developed a Cox multivariate model to predict the survival of stage II and III colorectal carcinoma patients from GSE39582 dataset
Forty-four regulator activities were detected to be correlated with survival, random forest was implemented for variable hunting
Summary
Colorectal carcinoma (CRC) is one of the most important causes of death worldwide [1]. The prognosis of colorectal cancer is controversial in stage II and III colorectal carcinoma [3]. The staging system is mature, some stage II colorectal adenocarcinoma patients have relatively poorer prognosis than stage III CRC patients. This indicates that clinical observations, including stage, could not distinguish the good or poor prognosis of colorectal carcinoma well in stage II/III CRC. Numerous molecular biomarkers have been reported to be able to predict the survival of stage II and III colorectal carcinoma patients [4,5,6,7,8]. The expression of genes, especially cancer-related genes, are regulated by critical signaling pathways and www.impactjournals.com/oncotarget
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