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结直肠癌中脂肪酸代谢的特征分析以指导临床治疗。

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

作者信息

Ding Chengsheng, Shan Zezhi, Li Mengcheng, Chen Hongqi, Li Xinxiang, Jin Zhiming

机构信息

Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

出版信息

Mol Ther Oncolytics. 2021 Feb 18;20:532-544. doi: 10.1016/j.omto.2021.02.010. eCollection 2021 Mar 26.

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.

摘要

结直肠癌(CRC)是最常见的恶性肿瘤之一,在全球36种癌症中死亡率排名第二。为探索潜在的治疗策略,对脂肪酸代谢在结直肠癌中的作用进行了研究。数据文件从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载。采用单因素和最小绝对收缩和选择算子(LASSO)Cox回归分析,构建了一个基于脂肪酸代谢相关基因的预后风险评分模型,用于预测结直肠癌的预后。在TCGA队列中,高风险评分患者的预后比低风险评分患者差,这一结果在GEO队列中得到了证实。使用“pRRophetic”R包进行的进一步分析表明,低风险患者对5-氟尿嘧啶更敏感。对预后风险评分模型与肿瘤微环境(TME)特征之间关联的综合评估表明,高风险患者适合激活I/II型干扰素(IFN)反应和促进炎症的功能。肿瘤免疫功能障碍与排除(TIDE)和SubMap算法结果也表明,高风险患者更适合抗CTLA4免疫治疗。因此,对脂肪酸代谢模式的评估有助于我们理解TME浸润特征,从而指导有效的免疫治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0a4/7941088/cecbed277358/fx1.jpg

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