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肥胖相关代谢基因 HSD17B8 可预防乳腺癌：高 RNA/蛋白表达预示更好的预后。

The Obesity-Related Metabolic Gene HSD17B8 Protects Against Breast Cancer: High RNA/Protein Expression Means a Better Prognosis.

机构信息

First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2022 Feb 20;28:e934424. doi: 10.12659/MSM.934424.

DOI:10.12659/MSM.934424
PMID:35184130
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8876026/
Abstract

BACKGROUND The incidence of breast cancer is increasing annually. Obesity and metabolism are considered risk factors for breast cancer. Discovery of obesity- and metabolism-related breast cancer prognostic genes is imminent. MATERIAL AND METHODS We screened metabolism-related genes (MRG) from KEGG and downloaded the obese female dataset GSE151839 from GEO, which screened differentially-expressed genes (DEGs), seen as female obesity-related genes. The intersection of MRGs and DEGs was obesity-related metabolic genes (OMGs), verified by enrichment analysis. After downloading breast cancer data from TCGA, univariate Cox regression and log-rank P analyses were used to screen hub OMGs related to breast cancer prognosis. ROC curve and Kaplan-Meier (KM) plotter, GEPIA, and GENT2 databases were used to verify the hub OMGs at the RNA level. CPTAC and HLA databases were used to verify the hub OMGs at the protein level. RESULTS We screened 33 OMGs. The results of univariate Cox regression and log-rank P analysis showed 3 of 33 OMGs (ABCA1, LPIN1, HSD17B8) were associated with the prognosis of breast cancer patients. After verification with ROC, KM-plotter, and GEPIA, only HSD17B8 was related to breast cancer prognosis (overall/disease-free survival). Results of GENT2 showed the RNA expression of HSD17B8 in breast cancer subtypes with poor prognosis is significantly lower than that with good prognosis. Results of CPTAC and HLA databases showed that the protein expression level of HSD17B8 in breast cancer tissues was significantly lower than that in adjacent normal tissues. CONCLUSIONS HSD17B8 is a protective gene against breast cancer. The higher the expression of HSD17B8, the better the prognosis of breast cancer patients.

摘要

背景

乳腺癌的发病率呈逐年上升趋势。肥胖和代谢被认为是乳腺癌的危险因素。因此，发现肥胖和代谢相关的乳腺癌预后基因迫在眉睫。

材料与方法

我们从 KEGG 中筛选出代谢相关基因（MRG），并从 GEO 下载肥胖女性数据集 GSE151839，该数据集筛选出差异表达基因（DEGs），这些基因被视为与女性肥胖相关的基因。MRG 和 DEG 的交集为肥胖相关代谢基因（OMGs），通过富集分析进行验证。从 TCGA 下载乳腺癌数据后，使用单变量 Cox 回归和对数秩 P 分析筛选与乳腺癌预后相关的关键 OMGs。使用 ROC 曲线和 Kaplan-Meier（KM）plotter、GEPIA 和 GENT2 数据库在 RNA 水平验证关键 OMGs。使用 CPTAC 和 HLA 数据库在蛋白质水平验证关键 OMGs。

结果

我们筛选出 33 个 OMGs。单变量 Cox 回归和对数秩 P 分析结果显示，33 个 OMGs 中的 3 个（ABCA1、LPIN1、HSD17B8）与乳腺癌患者的预后相关。经过 ROC、KM-plotter 和 GEPIA 验证后，只有 HSD17B8 与乳腺癌的预后相关（总生存/无病生存）。GENT2 的结果显示，HSD17B8 在预后不良的乳腺癌亚型中的 RNA 表达显著低于预后良好的亚型。CPTAC 和 HLA 数据库的结果表明，HSD17B8 蛋白在乳腺癌组织中的表达水平明显低于邻近正常组织。

结论

HSD17B8 是乳腺癌的保护性基因。HSD17B8 的表达水平越高，乳腺癌患者的预后越好。

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