Abstract

Background and aimLipid metabolic reprogramming is considered to be a new hallmark of malignant tumors. The purpose of this study was to explore the expression profiles of lipid metabolism-related genes (LMRG) in colorectal cancer (CRC).MethodsThe lipid metabolism statuses of 500 CRC patients from the Cancer Genome Atlas (TCGA) and 523 from the Gene Expression Omnibus (GEO GSE39582) database were analyzed. The risk signature was constructed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression.ResultsA novel four-LMRG signature (PROCA1, CCKBR, CPT2, and FDFT1) was constructed to predict clinical outcomes in CRC patients. The risk signature was shown to be an independent prognostic factor for CRC and was associated with tumour malignancy. Principal components analysis demonstrated that the risk signature could distinguish between low- and high-risk patients. There were significantly differences in abundances of tumor-infiltrating immune cells and mutational landscape between the two risk groups. Patients in the low-risk group were more likely to have higher tumor mutational burden, stem cell characteristics, and higher PD-L1 expression levels. Furthermore, a genomic-clinicopathologic nomogram was established and shown to be a more effective risk stratification tool than any clinical parameter alone.ConclusionsThis study demonstrated the prognostic value of LMRG and showed that they may be partially involved in the suppressive immune microenvironment formation.

Highlights

  • Background and aimLipid metabolic reprogramming is considered to be a new hallmark of malignant tumors

  • The present study aimed to develop a novel risk signature based on lipid metabolism-related genes (LMRG) to provide additional information for use in risk assessment and clinical decision-making in colorectal cancer (CRC)

  • Identification of differentially expressed and prognosisrelated genes in LMRG Expression data of LMRG were extracted from the the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts

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Summary

Introduction

Lipid metabolic reprogramming is considered to be a new hallmark of malignant tumors. The purpose of this study was to explore the expression profiles of lipid metabolism-related genes (LMRG) in colorectal cancer (CRC). Colorectal cancer (CRC) has the third highest incidence among malignancies worldwide and is the second most common cause of cancer-related deaths [1]. As the most common gastrointestinal malignancy, CRC is associated with well-known risk factors, including poor dietary. Other predictive factors include pathological type, differentiation degree and microvascular/serosa invasion, etc. These clinicopathological biomarkers cannot provide precise prognostic guidelines as they do not fully capture disease information. Molecular characteristics of tumors need to be included in new prognostic risk models

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