Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Aging (Albany NY). 2020 Nov 16;12(24):24983-24994. doi: 10.18632/aging.103806.
Metabolic change is the hallmark of cancer. In the present study, we aimed to develop a glycolysis-related gene signature to predict the prognosis of breast cancer patients. Gene expression profiles and clinical data of breast cancer patients were obtained from the GEO database. A four-gene based signature (ALDH2, PRKACB, STMN1 and ZNF292) was developed to separate patients into high-risk and low-risk groups. Patients in the low-risk group had significantly better prognosis than those in the high-risk group. Time-dependent ROC analysis demonstrated that the glycolysis-related gene signature had excellent prognostic accuracy. We further confirmed the expression of the four prognostic genes in breast cancer and paracancerous tissue samples using qRT-PCR analysis. Expression level of PRKACB was higher in paracancerous tissues, while STMN1 and ZNF292 were overexpressed in tumor samples, no significant difference was observed in ALDH2 expression level. Global proteome data of 105 TCGA breast cancer samples obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to evaluate the prognostic value in protein levels. Consistently, high expression level of PRKACB protein was associated with favorable prognosis, while high ZNF292 and STMN1 protein expression levels indicated poor prognosis. The glycolysis-related gene signature might provide an effective prognostic predictor and a new insight for individualize management of breast cancer patients.
代谢改变是癌症的标志。在本研究中，我们旨在开发一个与糖酵解相关的基因特征，以预测乳腺癌患者的预后。从 GEO 数据库中获取了乳腺癌患者的基因表达谱和临床数据。开发了一个基于四个基因的特征（ALDH2、PRKACB、STMN1 和 ZNF292），将患者分为高风险组和低风险组。低风险组患者的预后明显好于高风险组患者。时间依赖性 ROC 分析表明，该糖酵解相关基因特征具有优异的预后准确性。我们进一步使用 qRT-PCR 分析证实了四个预后基因在乳腺癌和癌旁组织样本中的表达。PRKACB 的表达水平在癌旁组织中较高，而 STMN1 和 ZNF292 在肿瘤样本中过表达，但 ALDH2 的表达水平没有明显差异。从临床蛋白质组肿瘤分析联盟 (CPTAC) 获得的 105 个 TCGA 乳腺癌样本的全蛋白质组数据用于评估蛋白质水平的预后价值。一致地，PRKACB 蛋白的高表达水平与良好的预后相关，而 ZNF292 和 STMN1 蛋白的高表达水平则预示着不良的预后。与糖酵解相关的基因特征可能为乳腺癌患者提供有效的预后预测指标，并为个体化管理提供新的见解。
