A lipid metabolism-related gene signature reveals dynamic immune infiltration of the colorectal adenoma-carcinoma sequence.

Background: Lipid metabolism-related genes (LMRGs) have been reported to be correlated with the immune infiltration of colorectal cancer (CRC). This study aimed to investigate the immune infiltration characteristics along the colorectal adenoma-carcinoma sequence (ACS) based on LMRGs.

Methods: Gene expression data of colorectal adenoma and carcinoma samples were obtained from the public databases. The "limma" package was applied to determine the differentially expressed LMRGs. Unsupervised consensus clustering was used to cluster colorectal samples. The features of the tumor microenvironment were analyzed by the "ESTIMATE", "GSVA", and "TIDE" algorithms.

Results: The expression of 149 differentially expressed LMRGs was defined as the LMRG signature. Based on this signature, the adenoma and carcinoma samples were divided into three clusters. Unexpectedly, these sequential clusters showed a directional relationship and collectively constituted the progressive course of colorectal ACS. Interestingly, the LMRG signature revealed that adenoma progression was accompanied by a progressive loss of immune infiltration and a stepwise establishment of a cold microenvironment, but carcinoma progression was characterized by a progressive gain of immune infiltration and a gradual establishment of a hot microenvironment.

Conclusions: The LMRG signature reveals dynamic immune infiltration along the colorectal ACS, which substantially changes the understanding of the tumor microenvironment of CRC carcinogenesis and provides novel insight into the role of lipid metabolism in this process.