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泛癌分析揭示了癌症中脂肪酸氧化调节因子的基因组学与临床结局之间的关联。

Pan-cancer analyses reveal genomics and clinical outcome association of the fatty acid oxidation regulators in cancer.

作者信息

Zhang Fu-Bin, Gan Lei, Zhu Tian-Hong, Ding Hui-Qing, Wu Cheng-Hao, Guan Yu-Tao, Chen Xue-Qin

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, China.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, No.389 Xincun Road, Shanghai, 200065, China.

出版信息

Heliyon. 2024 Mar 23;10(7):e28441. doi: 10.1016/j.heliyon.2024.e28441. eCollection 2024 Apr 15.

DOI:10.1016/j.heliyon.2024.e28441
PMID:38590909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10999922/
Abstract

BACKGROUND

Fatty acid oxidation (FAO) is considered to play a vital part in tumor metabolic reprogramming. But the comprehensive description of FAO dysregulation in tumors has not been unknown.

METHODS

We obtained FAO genes, RNA-seq data and clinical information from the Msigdb, TCGA and GTEx databases. We assessed their prognosis value using univariate cox analysis, survival analysis and Kaplan-Meier curve. We determined the function of FAO genes using gene set variation analysis. The correlation analysis was calculated by corrplot R package. Immunotherapy response was assessed through TIDE scores. The protein expression levels of FAO genes were validated using immunohistochemistry (IHC).

RESULTS

The FAO scores were highest in COAD but lowest in PCPG. FAO scores were significantly associated with the prognosis of some cancers in OS, DSS, DFI and PFI. Besides, gene set variation analysis identified that FAO scores were related to immune-related pathways, and immune infiltration analysis showed FAO scores were positively related to cancer-associated fibroblasts and various immune-related genes. TIDE scores were significantly decreased in ACC, CHOL, ESCA, GBM, LAML, SARC, SKCM and THCA compared with normal samples, while it was significantly increased in BLCA, LUAD, LUSC, PCPG, PRAD and STAD. Besides, most FAO genes were downregulated in pan-cancer compared with normal samples. Moreover, we found copy number variation (CNV) of FAO genes played a positive role in their mRNA expression, while methylation was negative. We determined FAO genes were closely related to some drugs in pan-cancer.

CONCLUSIONS

FAO score is a novel and promising factor for predicting outcomes.

摘要

背景

脂肪酸氧化（FAO）被认为在肿瘤代谢重编程中起关键作用。但肿瘤中FAO失调的全面描述尚不明确。

方法

我们从Msigdb、TCGA和GTEx数据库中获取了FAO基因、RNA测序数据和临床信息。我们使用单变量cox分析、生存分析和Kaplan-Meier曲线评估它们的预后价值。我们使用基因集变异分析确定FAO基因的功能。相关性分析通过R包corrplot计算。通过TIDE评分评估免疫治疗反应。使用免疫组织化学（IHC）验证FAO基因的蛋白表达水平。

结果

FAO评分在结肠癌（COAD）中最高，但在嗜铬细胞瘤（PCPG）中最低。FAO评分在总生存期（OS）、疾病特异性生存期（DSS）、无病生存期（DFI）和无进展生存期（PFI）方面与某些癌症的预后显著相关。此外，基因集变异分析表明FAO评分与免疫相关途径有关，免疫浸润分析显示FAO评分与癌症相关成纤维细胞和各种免疫相关基因呈正相关。与正常样本相比，在肾上腺皮质癌（ACC）、胆管癌（CHOL）、食管癌（ESCA）、胶质母细胞瘤（GBM）、急性髓系白血病（LAML）、肉瘤（SARC）、皮肤黑色素瘤（SKCM）和甲状腺癌（THCA）中TIDE评分显著降低，而在膀胱癌（BLCA）、肺腺癌（LUAD）、肺鳞癌（LUSC）、嗜铬细胞瘤（PCPG）、前列腺癌（PRAD）和胃癌（STAD）中显著升高。此外，与正常样本相比，大多数FAO基因在泛癌中表达下调。此外，我们发现FAO基因的拷贝数变异（CNV）对其mRNA表达起积极作用，而甲基化则起消极作用。我们确定FAO基因在泛癌中与某些药物密切相关。

结论

FAO评分是预测预后的一个新的且有前景的因素。

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