Prognostic and immune infiltration signatures of proteasome 26S subunit, non-ATPase (PSMD) family genes in breast cancer patients

Abstract

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.

Single-cell transcriptomics of neuroblastoma identifies chemoresistance-associated genes and pathways

“…Furthermore, we also observed several genes belonging to Histone H1 axis, known to be a therapeutic target in cancer cell self-renewal [49] . Interestingly, in etoposide resistant clusters we found numerous genes belonging to PSMB , PSMC , and PSMD proteasome-subunit families, known to confer drug resistance in diverse cancers [50] , [51] , [52] .…”

Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma

“…The findings indicate that compared with high immune cell infiltration, patients with low immune cell infiltration levels may appear poor outcomes to conventional therapy in some solid tumors ( Tobin et al, 2019 ). A paper from reported that the expression of PSMD member genes including PSMD2 is related to markers of six tumor-infiltrating immune cell types in breast cancer Xuan et al (2021) . In this study, we analyzed the correlation between the expression of PSMD2 and immune cell infiltration.…”

“…However, the number of lung cancer patients enrolled in this study was relatively small. Moreover, PSMD family genes are reported to correlate with immune infiltration profiles in breast cancer ( Xuan et al, 2021 ). Up to now, there is no studies have designed to investigate the association between PSMD2 expression and immune cell infiltration in lung adenocarcinoma.…”

Decoupling of mRNA and protein expression in aging brains reveals the age-dependent adaptation of specific gene subsets

“…We identified 208 proteins differentially enriched in the aging cortex ( Figure 4A ) and showed that 79% of these proteins (164/208) were involved in catabolic and metabolic processes such as the proteasome complex ( Figure 4C ). PSMD and PSMC proteins, which are proteasome 26S subunits involved in the degradation of misfolded and abnormal proteins (Kao et al 2021; Xuan et al 2021), were specifically enriched in this subset ( Supplemental Table 1 ). It was reported that damaged and misfolded proteins tend to accumulate during the brain aging process, and that the proteasome is responsible for the degradation of these proteins (Carrard et al 2002; Keller, Gee, and Ding 2002; Saez and Vilchez 2014).…”