A NOD-Like Receptor Signaling-Based Gene Signature Identified as a Novel Prognostic Biomarker for Predicting Overall Survival of Colorectal Cancer Patients

Background: Colorectal Cancer (CRC) is the most frequently diagnosed gastrointestinal tract malignant tumor worldwide, which is closely associated with distant metastasis and poor prognosis. Due to high degree of heterogeneity, reliable prognostic biomarkers are urgently needed to guide the therapeutic intervention of CRC patients. Objective: The present study aimed to develop a NOD-Like Receptors (NLRs) signaling-based gene signature that can successfully predict the overall survival of CRC patients. Methods: Firstly, differentially expressed NLR signaling-related genes were identified between primary and metastatic human CRC samples. Genes with prognostic value were then screened through univariate Cox regression analysis. Next, the NLR signaling-based prognostic signature was constructed by LASSO-penalized Cox regression analysis, and its predictive ability was further confirmed in an independent cohort. Furthermore, functional studies including GO, GSEA, ssGSEA and chemotherapeutic response analyses were performed to explore the role of the NLR signaling-based signature in CRC pathogenesis and therapy. Results: The established prognostic signature that consisted of 7 NLR signaling-related genes can effectively stratify the high-risk and low-risk CRC patients in both training and validation cohorts. Moreover, the signature proved to be an independent indicator of overall survival in CRC patients. Functional annotation and chemotherapeutic response analyses showed that the signature was closely associated with immune status and chemotherapeutic sensitivity of CRC patients. Conclusion: The novel NLR signaling-based gene signature could serve as a potential tool for survival prediction and therapeutic evaluation, thereby contributing to the personalized prognostic management of CRC patients.