Rectum adenocarcinoma metabolic subtypes analysis and a risk prognostic model construction based on fatty acid metabolism genes.

Abstract

Fatty acid metabolism is an essential part of cancer research due to its role in cancer initiation and progression. However, its characteristics and prognostic value in rectum adenocarcinoma have not been systematically evaluated. We collected fatty acid metabolism gene expression profiles and clinical information from the cancer genome atlas and gene expression omnibus databases. After excluding individuals lacking clinical information and the presence of genetic mutations, we performed consistent clustering of the remaining patients and selected stable clustering results to group patients. Differentially expressed genes and gene set enrichment analysis were compared between subgroups, while metabolic signature identification and decoding the tumor microenvironment were performed. In addition, we explored the survival status of patients among different subgroups and identified signature genes affecting survival by least absolute shrinkage and selection operator regression. Finally, we selected signature genes to construct a risk prognostic model by multivariate Cox regression and evaluated model efficacy by univariate Cox regression and the receiver operating characteristic curve. By consensus clustering, patients were distinguished into 2 stable subpopulations, gene set enrichment analysis and metabolic signature identification effectively defined 2 completely different subtypes of fatty acid metabolism: fatty acid catabolic subtype and fatty acid anabolic subtype. Among them, patients with the fatty acid catabolic subtype had a poorer prognosis, with a significantly lower proportion of myeloid dendritic cells infiltration within the tumor microenvironment. Aquaporin 7 (hazard ratio, HR = 2.064 (1.4408-4.5038); P < .01), X inactive specific transcript (HR = (0.3758-0.7564), P = .045) and interleukin 4 induced 1 (HR = 1.34 (1.13-1.59); P = .034), were selected by multivariate Cox regression, which constructed a risk prognostic model. The independent hazard ratio of the model was 2.72 and the area under curve was higher than age, gender and tumor stage, showing better predictive efficacy. Our study revealed the heterogeneity of fatty acid metabolism in rectum adenocarcinoma, defined 2 completely distinct subtypes of fatty acid metabolism, and finally established a novel fatty acid metabolism-related risk prognostic model. The study contributes to the early risk assessment and monitoring of individual prognosis and provides data to support individualized patient treatment.