Identification of a novel lipid metabolism-related gene signature for predicting colorectal cancer survival

Abstract

Colorectal cancer (CRC) is a common malignant tumor worldwide. Lipid metabolism is a prerequisite for the growth, proliferation and invasion of cancer cells. However, the lipid metabolism-related gene signature and its underlying molecular mechanisms remain unclear. The aim of this study was to establish a lipid metabolism signature risk model for survival prediction in CRC and to investigate the effect of gene signature on the immune microenvironment. Lipid metabolism-mediated genes (LMGs) were obtained from the Molecular Signatures Database. The consensus molecular subtypes were established using “ConsensusClusterPlus” based on LMGs and the cancer genome atlas (TCGA) data. The risk model was established using univariate and multivariate Cox regression with TCGA database and independently validated in the international cancer genome consortium (ICGC) datasets. Immune infiltration in the risk model was developed using CIBERSORT and xCell analyses. A total of 267 differentially expressed genes (DEGs) were identified between subtype 1 and subtype 2 from consensus molecular subtypes, including 153 upregulated DEGs and 114 downregulated DEGs. 21 DEGs associated with overall survival (OS) were selected using univariate Cox regression analysis. Furthermore, a prognostic risk model was constructed using the risk coefficients and gene expression of eleven-gene signature. Patients with a high-risk score had poorer OS compared with patients in the low-risk score group (p = 3.36e-07) in the TCGA cohort and the validationdatasets (p = 4.03e-05). Analysis of immune infiltration identified multiple T cells were associated with better prognosis in the low-risk group, including Th2 cells (p = 0.0208), regulatory T cells (p = 0.0425), and gammadelta T cells (p = 0.0112). A nomogram integrating the risk model and clinical characteristics was further developed to predict the prognosis of patients with CRC. In conclusion, our study revealed that the expression of lipid-metabolism genes were correlated with the immune microenvironment. The eleven-gene signature might be useful for prediction the prognosis of CRC patients.

Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer

“…Our signature exhibits a diagnostic performance that is similar to that of the signature associated with lipid metabolism. 46 …”

“…Our signature exhibits a diagnostic performance that is similar to that of the signature associated with lipid metabolism. 46 The role of TENT5C in the development and progression of colon cancer is not well understood. To gain further insight into the biological function of TENT5C in colon cancer, we categorized colon cancer patients into two subgroups based on their TENT5C expression levels: high and low.…”

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

“…Tumor heterogeneity shapes the tumor microenvironment and plays decisive roles in tumor initiation, progression, and drug resistance [ 9 ]. Several studies have provided novel insight into lipid metabolic heterogeneity in CRC based on lipid metabolism-related genes (LMRGs) and reported that the LMRGs were associated with immune infiltration and were useful for predicting the prognosis of CRC patients [ 10 – 12 ]. However, no study has focused on the role of LMRGs in the complete course of the colorectal ACS.…”

Investigation of potential prognostic biomarkers for colorectal cancer

“…According to statistics, in 2008, there were nearly 150,000 newly diagnosed cases and 50,000 deaths [6]. By 2012, the Global Cancer Observatory estimated that 1.3 million new cases were diagnosed with CRC and nearly 700,000 patients died from it [7]. CRC is more common in Western countries, accounting for more than 65% of cases [8].…”