Prognostic and Genomic Analysis of Proteasome 20S Subunit Alpha (PSMA) Family Members in Breast Cancer

Abstract

The complexity of breast cancer includes many interacting biological processes, and proteasome alpha (PSMA) subunits are reported to be involved in many cancerous diseases, although the transcriptomic expression of this gene family in breast cancer still needs to be more thoroughly investigated. Consequently, we used a holistic bioinformatics approach to study the PSMA genes involved in breast cancer by integrating several well-established high-throughput databases and tools, such as cBioPortal, Oncomine, and the Kaplan–Meier plotter. Additionally, correlations of breast cancer patient survival and PSMA messenger RNA expressions were also studied. The results demonstrated that breast cancer tissues had higher expression levels of PSMA genes compared to normal breast tissues. Furthermore, PSMA2, PSMA3, PSMA4, PSMA6, and PSMA7 showed high expression levels, which were correlated with poor survival of breast cancer patients. In contrast, PSMA5 and PSMA8 had high expression levels, which were associated with good prognoses. We also found that PSMA family genes were positively correlated with the cell cycle, ubiquinone metabolism, oxidative stress, and immune response signaling, including antigen presentation by major histocompatibility class, interferon-gamma, and the cluster of differentiation signaling. Collectively, these findings suggest that PSMA genes have the potential to serve as novel biomarkers and therapeutic targets for breast cancer. Nevertheless, the bioinformatic results from the present study would be strengthened with experimental validation in the future by prospective studies on the underlying biological mechanisms of PSMA genes and breast cancer.

Analysis of the Prognostic Significance and Immune Infiltration of the Amino Acid Metabolism-Related Genes in Colon Adenocarcinoma

“…Meanwhile, this matches the result of the disruption of the T-cell methionine metabolic pathway by tumor cells ( Bian et al, 2020 ). Furthermore, PSMA8 predicts favorable outcomes in cancer and is associated with immune response signaling, which corresponded with our study ( Chiao et al, 2021 ). In addition, PSMB2 shares the same conclusion with PSMA8.…”

CanSig: discovery of shared transcriptional states across cancer patients from single-cell RNA sequencing data

“…Some of the strongest gains in 15q included TMED3, IMP3, PSMA4 and RCN1 . In the context of breast cancer, TMED3 and RCN1 overexpression promote proliferation 48,49 , IMP3 is associated with EMT 50 and PSMA4 correlated with poorer survival 51 . The basal phenotype in breast cancer is an aggressive type associated with poor prognosis, that typically expresses genes associated with proliferation 52 and EMT 53 .…”

Genetic insights into therapeutic targets for aortic aneurysms: A Mendelian randomization study

“…Proteasome dysfunction leads to many cardiovascular diseases, including cardiomyopathies, heart failure, and atherosclerosis. 46 , 47 In aneurysms, proteasome peptidase activity was increased in both human and mouse abdominal AA tissue, which could be inhibited by bortezomib, a potent, selective inhibitor of the chymotrypsin-like activity of the 20S proteasome. Additionally, studies have demonstrated that low-dose bortezomib injection appeared to reduce MMP activity, smooth muscle cell phenotypic switching, and elastin degradation, resulting in the attenuation of aneurysm formation.…”