Crosstalk of lactate metabolism-related subtypes, establishment of a prognostic signature and immune infiltration characteristics in colon adenocarcinoma

Colon adenocarcinoma (COAD) is a common malignant tumor of digestive tract and lactate metabolism has been linked to tumor development and progression. In this study, we sought to investigate the influence of lactate metabolism-related genes (LRGs) prognosis. We also aimed to identify distinct LRG-related clusters and develop a risk signature for assessing patient prognosis, immunological characteristics, and response to therapy. We analyzed data from The Cancer Genome Atlas (TCGA) to reveal the expression and mutational features of LRGs in COAD patients. In the integrated TCGA and GSE39582 cohort, consensus clustering analysis was employed to classify patients into two distinct LRG-related clusters. Using differentially expressed genes (DRGs) from these two clusters, we established a LRG-related gene cluster and prognostic signature which was used to classify patients into high-risk and low-risk groups. An validation cohort was used to validate the predictive ability of risk signature and expression of 6 candidate LRGs was confirmed through quantitative real-time PCR (qRT-PCR). Nomograms were created to visually represent the clinical value of LRG-related signature. Furthermore, we extensively examined differences in immune cell infiltration, tumor mutational load (TMB), microsatellite instability (MSI) and drug sensitivity between two risk groups. Analysis of the integrated TCGA and GSE39582 cohorts revealed two distinct LRG-related clusters and gene clusters with significant differences in overall survival (OS) and tumor microenvironment. We developed a LRG-related signature comprising 6 candidate LRGs that reliably predicted OS and qRT-PCR validation confirmed the expression of LRGs. Based on the median risk score, patients were divided into low-risk and high-risk groups, with low-risk group showing better survival. Furthermore, patients in high-risk group were more sensitive to chemotherapy and associated with higher TMB, higher proportion of MSI-H. Our study provides a valuable method for guiding clinical management and personalized treatment of COAD patients, which offers new insights into individualized treatment strategies, ultimately improving patient outcomes.