Abstract
Backgroud
The biological function of neurotransmitter receptor-related genes (NRGs) has been increasingly appreciated in cancer. However, the relationship between neurotransmitters and colorectal cancer (CRC) was not well understood. The purpose of this study was to develop a neurotransmitter-related signature for risk stratification and prognosis prediction in CRC.
Methods
The RNA-seq data of CRC and clinical information of corresponding samples were obtained from the UCSC-Xena platform. GSE33113 databases are used as a validation cohort. The NRGs were obtained from the literature and Genecards database. Univariate Cox regression and Lasso regression were used to identify differentially expressed genes (DEGs) and establish neurotransmitter-related prognosis signatures. A nomogram was constructed, and its performance was evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA). A total of 221 neurotransmitter-related DEGs were identified. Univariate Cox regression analysis identified the 10 best prognostic genes as risk signatures, and the Kaplan-Meier curve, ROC curve, and risk plot verified its performance in TCGA and GSE33113 cohorts.
Results
A prognostic nomogram was developed incorporating risk score, age, and TNM stage, with ROC and DCA curves demonstrating its strong prognostic capability. Furthermore, high-risk scores were found to be significantly associated with invasions and stages. The high-risk group exhibited activation of the angiogenesis, apical junction, coagulation, epithelial-mesenchymal transition, and myogenesis pathways. T In terms of drug sensitivity, TIDE scores were significantly lower in the low-risk group, which was more suitable for immunotherapy. Chemotherapy, antivascular, and targeted therapies may be more appropriate for high-risk patients. Neurotransmitter-based prognostic signatures were found in our investigation, and our 10-gene risk panel is a useful biomarker for predictive risk assessment in CRC patients.