Prognostic effect of inflammatory genes on stage I-III colorectal cancer – integrative analysis of TCGA data

Abstract

Background Inflammatory status indicators have been reported as a prognostic biomarker of colorectal cancer (CRC). However, since the inflammatory interactions with colon involve various modes of action, the biological mechanism to link inflammation and CRC prognosis is not fully elucidated. We comprehensively evaluated the predictive role of the expression and methylation level of inflammation-related genes for CRC prognosis and their pathophysiological associations. Method An integrative analysis was conducted on 247 patients of stage I-III CRC from The Cancer Genome Atlas. Lasso-penalized Cox proportional hazards regression (Lasso-Cox) and statistical Cox proportional hazard regression (CPH) were used for analysis. Result Models to predict overall survival were designed with respective combinations of clinical variables, including age, sex, stage, gene expression, and methylation. An integrative model combining expression, methylation, and clinical features had the highest performance (median C-index=0.756), compared to the model with clinical features alone (median C-index=0.726). By multivariate CPH with features from the best model, methylation levels of CEP250, RAB21 and TNPO3 were significantly associated with overall survival. They did not share any biological process in functional networks. The 5-year survival rate was 29.8% in a low methylation group of CEP250 and 79.1% in a high (P <0.001). Conclusion Our study result implicates the importance of integrating the expression and methylation information along with clinical information in prediction of survival. CEP250, RAB21 and TNPO3, in the prediction model might have a crucial role in CRC prognosis and further improve our understanding of potential mechanisms linking inflammatory reaction and CRC progression.

Combined detection of preoperative neutrophil to lymphocyte ratio and interleukin-6 as an independent prognostic factor for patients with non-metastatic colorectal cancer

“…In the early immune response, inflammation may inhibit tumorigenesis; however, persistent inflammatory stimulation can promote tumor progression (11). Some inflammatory biomarkers have the ability to predict the prognosis of CRC (12,13). Neutrophils play a central role in inflammation within the tumor as they are attracted by CXCR2 ligands like CXCL1, CXCL2 and CXCL5, among others.…”

Combined Detection of Preoperative Neutrophil to Lymphocyte Ratio and Interleukin-6 as an Independent Prognostic Factor for Patients with Non-Metastatic Colorectal Cancer

“…In the early immune response, inflammation may inhibit tumorigenesis, but persistent inflammatory stimulation can promote tumor progression [8]. Some inflammatory biomarkers are associated with poor clinical outcomes of CRC and have the ability to predict the prognosis of CRC [9,10]. NLR which calculated by dividing the neutrophil count by the lymphocyte count has been proposed as an indicator of cancer-related inflammation [11].…”