4.5 Article

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

期刊

MOLECULAR THERAPY-ONCOLYTICS
卷 20, 期 -, 页码 532-544

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CELL PRESS
DOI: 10.1016/j.omto.2021.02.010

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资金

  1. Science and Technology Commission of Shanghai Municipality [16140900302]

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The study investigated the role of fatty acid metabolism in colorectal cancer (CRC) and established a prognostic risk score model based on fatty acid metabolism-related genes. The model can predict the prognosis of CRC patients and guide effective immunotherapy regimens.
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.

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