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生物信息学分析鉴定出脂肪酸代谢相关基因风险-signature 与胶质瘤的恶性程度、预后和免疫表型相关。

Bioinformatic Profiling Identifies a Fatty Acid Metabolism-Related Gene Risk Signature for Malignancy, Prognosis, and Immune Phenotype of Glioma.

机构信息

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.

Immunology Laboratory, Neurosurgical Institute of Fudan University, Shanghai 200040, China.

出版信息

Dis Markers. 2019 Dec 4;2019:3917040. doi: 10.1155/2019/3917040. eCollection 2019.

Abstract

Cancer cells commonly have metabolic abnormalities. Aside from altered glucose and amino acid metabolism, cancers cells often share the attribute of fatty acid metabolic alterations. However, fatty acid metabolism related-gene set has not been systematically investigated in gliomas. Here, we provide a bioinformatic profiling of the fatty acid catabolic metabolism-related gene risk signature for the malignancy, prognosis and immune phenotype of glioma. In this study, a cohort of 325 patients with whole genome RNA-seq expression data from the Chinese Glioma Genome Atlas (CGGA) dataset was used as training set, while another cohort of 667 patients from The Cancer Genome Atlas (TCGA) dataset was used as validating set. After confirmed that fatty acid catabolic metabolism-related gene set could distinguish clinicopathological features of gliomas, we used LASSO regression analysis to develop a fatty-acid metabolism-related gene risk signature for glioma. This 8-gene risk signature was found to be a good predictor of clinical and molecular features involved in the malignancy of gliomas. We also identified that this 8-gene risk signature had high prognostic values in patients with gliomas. Correlation analysis showed that our risk signature was closely associated with the immune cells involved in the microenvironment of glioma. Furthermore, the fatty acid catabolic metabolism-related gene risk signature was also found to be significantly correlated with immune checkpoint members and . In summary, we have identified a fatty acid metabolism-related gene risk signature for malignancy, prognosis, and immune phenotype of glioma; and our study might contribute to better understanding of metabolic pathways and further developing of novel therapeutic approaches for gliomas.

摘要

癌细胞通常存在代谢异常。除了葡萄糖和氨基酸代谢改变外,癌细胞通常还具有脂肪酸代谢改变的特征。然而,脂肪酸代谢相关基因集在神经胶质瘤中尚未得到系统研究。在这里,我们提供了一个与胶质瘤恶性程度、预后和免疫表型相关的脂肪酸分解代谢相关基因风险特征的生物信息学分析。在这项研究中,我们使用来自中国神经胶质瘤基因组图谱(CGGA)数据集的 325 名患者的全基因组 RNA-seq 表达数据作为训练集,同时使用来自癌症基因组图谱(TCGA)数据集的 667 名患者作为验证集。在证实脂肪酸分解代谢相关基因集可以区分神经胶质瘤的临床病理特征后,我们使用 LASSO 回归分析来开发神经胶质瘤的脂肪酸代谢相关基因风险特征。该 8 个基因风险特征被发现是神经胶质瘤恶性特征的临床和分子特征的良好预测因子。我们还发现,该 8 个基因风险特征在神经胶质瘤患者中具有较高的预后价值。相关性分析表明,我们的风险特征与胶质瘤微环境中涉及的免疫细胞密切相关。此外,脂肪酸分解代谢相关基因风险特征还与免疫检查点成员和显著相关。总之,我们已经确定了一个与神经胶质瘤恶性程度、预后和免疫表型相关的脂肪酸代谢相关基因风险特征;我们的研究可能有助于更好地理解代谢途径,并为神经胶质瘤的治疗方法提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bca/6914924/c8036aa96bd0/DM2019-3917040.001.jpg

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