A robust panel based on tumour microenvironment genes for prognostic prediction and tailoring therapies in stage I–III colon cancer

Abstract

Background: Tumour microenvironment (TME)is critical for the regulation of cancer development as well as therapy. The objective of the current study was the development of a robust prognostic model based on TME-relevant genes. Methods: Five public microarray datasets providing clinical information were obtained. The least absolute shrinkage and selection operator regression method was used to reduce the dimensionality of robust prognostic genes identified via the bootstrap method. Findings: We established a prognostic panel, designated as tumour microenvironment risk score (TMRS), consisting of 100 genes. With specific risk score formulae, the TMRS panel possesses a strong ability to predict relapse-free survival and overall survival through both univariate and multivariate analyses. Compared with the TNM stage, the TMRS panel showed much higher predictive accuracy. Further analysis revealed that patients with higher TMRS scores exhibited no therapeutic benefits from adjuvant chemotherapy, probably due to the activation of stromal relevant pathways and infiltration of stromal cells. Besides colon cancer, the TMRS panel was also revealed to be a reliable tool for prognostic prediction and chemotherapeutic decision-making in gastric cancer. Its value in predicting immunotherapy outcomes was also confirmed in two other cohorts consisting of metastatic urothelial carcinoma patients and melanoma patients. Interpretation: Our TMRS panel may be an effective tool for survival prediction and treatment guidance in patients with stage I–III colon cancer. Fund: This work was supported by the National Natural Science Foundation of China (No. 81772580)and Guangzhou Planed Project of Science and Technology (No. 201803010070).