Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Division of Neurosurgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Aging (Albany NY). 2021 Nov 28;13(22):24882-24913. doi: 10.18632/aging.203722.
The complexity of breast cancer includes many interacting biological processes that make it difficult to find appropriate therapeutic treatments. Therefore, identifying potential diagnostic and prognostic biomarkers is urgently needed. Previous studies demonstrated that 26S proteasome delta subunit, non-ATPase (PSMD) family members significantly contribute to the degradation of damaged, misfolded, abnormal, and foreign proteins. However, transcriptional expressions of PSMD family genes in breast cancer still remain largely unexplored. Consequently, we used a holistic bioinformatics approach to explore PSMD genes involved in breast cancer patients by integrating several high-throughput databases, including The Cancer Genome Atlas (TCGA), cBioPortal, Oncomine, and Kaplan-Meier plotter. These data demonstrated that PSMD1, PSMD2, PSMD3, PSMD7, PSMD10, PSMD12, and PSMD14 were expressed at significantly higher levels in breast cancer tissue compared to normal tissues. Notably, the increased expressions of PSMD family genes were correlated with poor prognoses of breast cancer patients, which suggests their roles in tumorigenesis. Meanwhile, network and pathway analyses also indicated that PSMD family genes were positively correlated with ubiquinone metabolism, immune system, and cell-cycle regulatory pathways. Collectively, this study revealed that PSMD family members are potential prognostic biomarkers for breast cancer progression and possible promising clinical therapeutic targets.
乳腺癌的复杂性包括许多相互作用的生物学过程，这使得寻找合适的治疗方法变得困难。因此，迫切需要鉴定潜在的诊断和预后生物标志物。先前的研究表明，26S 蛋白酶体 δ 亚基，非-ATP 酶（PSMD）家族成员在降解损伤、错误折叠、异常和外来蛋白质方面起着重要作用。然而，PSMD 家族基因在乳腺癌中的转录表达仍在很大程度上尚未被探索。因此，我们使用整体生物信息学方法，通过整合包括癌症基因组图谱（TCGA）、cBioPortal、Oncomine 和 Kaplan-Meier plotter 在内的几个高通量数据库，来探索参与乳腺癌患者的 PSMD 基因。这些数据表明，PSMD1、PSMD2、PSMD3、PSMD7、PSMD10、PSMD12 和 PSMD14 在乳腺癌组织中的表达水平明显高于正常组织。值得注意的是，PSMD 家族基因的表达增加与乳腺癌患者的预后不良相关，这表明它们在肿瘤发生中起作用。同时，网络和通路分析也表明，PSMD 家族基因与泛醌代谢、免疫系统和细胞周期调控途径呈正相关。总的来说，这项研究揭示了 PSMD 家族成员是乳腺癌进展的潜在预后生物标志物，也是有希望的临床治疗靶点。
