Characterization of the fatty acid metabolism in colorectal cancer to guide clinical therapy

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors, with the second-highest mortality of all 36 cancers worldwide. The roles of fatty acid metabolism in CRC were investigated to explore potential therapeutic strategies. The data files were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a prognostic risk score model with fatty acid metabolism-related genes for predicting prognosis in CRC. Patients with a high-risk score had a poorer prognosis in TCGA cohort than those with a low-risk score and were confirmed in the GEO cohort. Further analysis using the “pRRophetic” R package revealed that low-risk patients were more sensitive to 5-fluorouracil. A comprehensive evaluation of the association between prognostic risk score model and tumor microenvironment (TME) characteristics showed that high-risk patients were suitable for activating a type I/II interferon (IFN) response and inflammation-promoting function. Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap algorithm results also demonstrated that high-risk patients are more suitable for anti-CTLA4 immunotherapy. Therefore, the evaluation of the fatty acid metabolism pattern promotes our comprehension of TME infiltration characteristics, thus guiding effective immunotherapy regimens.

The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

“…The R package “Prophetic” was used to analyze the drug sensitivity analysis of samples from different risk groups ( Ding et al, 2021 ). Combined with the relevant data downloaded from the CellMiner Database, the correlation analysis of drug sensitivity and the expression level of 6 m 6 A/m 5 C/m 1 A-related lncRNAs was further carried out ( Xu X. et al, 2020 ).…”

Fatty Acid Metabolism-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Patients With Colorectal Cancer

“…Therefore, the exploration of the underlying molecular mechanisms and the discovery of reliable prognostic biomarkers are urgent for improving prognosis evaluation and individualized treatment. Following in-depth studies of metabolic reprogramming, researchers gradually realized the importance of fatty acid metabolism in CRC ( 11 , 13 , 30 , 31 ). However, our understanding of the association between lncRNA and fatty acid metabolism in CRC is limited.…”

“…In oncogenesis, fatty acids are needed to store energy, synthesize membranes, and produce signaling molecules ( 12 ). It has shown that the decipherment of the fatty acid metabolism and molecular mechanism of CRC will lead to identifying novel therapeutic targets, thus developing effective treatment methods ( 13 , 14 ). Wang et al.…”

“…In oncogenesis, fatty acids are needed to store energy, synthesize membranes, and produce signaling molecules (12). It has shown that the decipherment of the fatty acid metabolism and molecular mechanism of CRC will lead to identifying novel therapeutic targets, thus developing effective treatment methods (13,14). Wang et al found that CPT1A-mediated fatty acid oxidation activation inhibits anoikis in CRC cells, which indicated that CPT1A is an attractive target to treat metastatic CRC (15).…”

Untargeted GC-MS-Based Metabolomics for Early Detection of Colorectal Cancer

“…Simultaneously, with the reduction of inositol, an inhibitor of cancer, the cancer cell grows faster. Therefore, inositol might be a useful tool to inhibit the development and progression of CRC ( 25 ).…”