Development of lactate‐related gene signature and prediction of overall survival and chemosensitivity in patients with colorectal cancer

Abstract

Background Colorectal cancer (CRC) is a malignant tumor of the digestive system that contains high levels of immune cells. Lactic acid, a major metabolite, plays a crucial role in tumor development, maintenance, and therapeutic response. However, the prognostic potential and therapeutic biomarker potential of lactate‐related genes (LRGs) in CRC patients remain to be elucidated. Methods We collected the mRNA expression profile and clinical data of CRC patients from the Cancer Genome Atlas (TCGA) database and the GSE59382 cohort. Univariate Cox regression, Lasso regression and multivariate Cox regression analysis were used to construct the prognosis model. Combined with the risk score and important clinicopathological features, the nomogram was established. In addition, the relationship between risk score and immune infiltration, immune checkpoint gene expression, and drug sensitivity was investigated. Results We constructed lactate‐related gene signatures (LRGS) based on four LRGs, which independently predicted the prognosis of CRC. Patients with different risk scores are found to have distinct immune status, tumor mutation load, immune response, and drug sensitivity. In addition, nomogram results determined by risk scores and clinical factors have higher predictive performance. Conclusion We found that LRGS is a reliable biomarker for predicting clinical outcomes, evaluating immune infiltration and efficacy, and predicting the sensitivity to drugs in patients with CRC.

Identification of Gut Microbiota Profile Associated with Colorectal Cancer in Saudi Population

“…In the absence of butyrate, colonocytes move from fatty acid metabolism to glucose metabolism, which results in an increase in lactate in the gut lumen [64]. Lactate encourages tumor growth and development by providing energy to tumor cells and evading immune defenses [18]. C. innocuum was one of the bacteria enriched in our CRC (Figure 3B).…”

“…Dysbiosis microbiota can generate a multitude of metabolites that play a significant role in the development of CRC. These include secondary bile acid [17], short chain fatty acid, SCFA, notably lactic acid, acetic acid and propionic acid [18,19], colibactin [20] trimethylamine/Trimethylamine-N-Oxide (TAM/TMAO) [21], and various others compounds. However, it is still unclear how the human gut microbiota and these metabolites contribute to the development of CRC.…”

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

“…By examining the protein expression patterns within tumors, researchers can identify signatures associated with disease aggressiveness, metastatic potential, and the likelihood of recurrence. 57 This information allows clinicians to predict patient outcomes more accurately and make informed decisions about the most suitable treatment strategies. Additionally, the identification of predictive protein markers can guide treatment choices, improving the efficacy of therapies, such as targeted agents or immunotherapies.…”

“…Proteomic studies also contribute to the discovery of prognostic and predictive markers in colorectal cancer. By examining the protein expression patterns within tumors, researchers can identify signatures associated with disease aggressiveness, metastatic potential, and the likelihood of recurrence . This information allows clinicians to predict patient outcomes more accurately and make informed decisions about the most suitable treatment strategies.…”