Identification of PSMD14 as a potential novel prognosis biomarker and therapeutic target for osteosarcoma

Abstract

Background: Osteosarcoma is the most common primary bone tumor. The survival rate of osteosarcoma patients has not significantly increased in the past decades.Uncovering the mechanisms of malignancy, progression, and metastasis will shed light on the development of new therapeutic targets and treatment for osteosarcoma. Aim:The aim of this study is to identify potential osteosarcoma biomarker and/or therapeutic targets by using integrated bioinformatics analysis. Methods and results:We utilized existing gene expression datasets to identify differential expressed genes (DEGs) that could serve as osteosarcoma biomarkers or even as therapeutic targets. We found 48 DEGs were overlapped in three datasets. Among these 48 DEGs, PSMD14 was on the top of the up-regulated gene list. We further found that higher PSMD14 expression was correlated with higher risk group (younger age group, ≤20.83 years of age), metastasis within 5 years and higher grade of tumor. Higher PSMD14 expression in osteosarcoma had positive correlation with higher infiltration of CD8+ T cells, neutrophils and myeloid dendritic cells. Kaplan-Myer survival data further revealed that higher expression of PSMD14 predicted significantly worse prognosis (p = .013). Gene set enrichment analysis was further performed for the DEGs related to PSMD14 in osteosarcoma. We found that lower PSMD14 expression group had more immune responses such as interferon γ, α responses, inflammation response etc. However, the higher PSMD14 expression group had more cell proliferation-related biological processes, such as G2M checkpoints and Myc targets. Through establishing protein-protein interaction networks using PSMD14 related DEGs, we identified 10 hub genes that were all ribosomal proteins. These hub genes may play roles in osteosarcoma tumorigenesis, progression and/or metastasis. Conclusion:We identified PSMD14 gene as a possible osteosarcoma biomarker, and/or a possible therapeutic target.

The prognostic role of PSMD14 in head and neck squamous cell carcinoma

“…Similarly, high expression of PSMD14 is associated with a worse prognosis in multiple myeloma, esophageal, ovarian, breast cancer and osteosarcoma. Although expression is associated with prognosis and occasionally with advanced cancer features in these studies, correction of the prognostic relevance of PSMD14 for potential confounders was not described (Lv et al 2019;Luo et al 2017;Song et al 2017;Sun et al 2021;Gong and Wei 2021). In accordance with our results, Zhang et al revealed that PSMD14 is associated with OS and DFS in lung adenocarcinoma.…”

Tandem Mass Tag-Based Proteomic Analysis of Normal and Degenerated Human Intervertebral Discs

“…The mechanism underlying the action of PSMD14 involves binding to a C-terminal isopeptide substrate to remove a polyubiquitin segment, thus promoting the transport of the substrate and degradation of the CP. 20 Although the proteasome system cannot degrade aggregated proteins, intriguingly, PSMD14 appears to exert a positive impact on autophagy function. 21 The cellular autophagy pathway is closely related to tumorigenesis, infection, neurodegenerative diseases and other diseases, whereas inhibition of cellular endocrine autophagy can delay the progression of these diseases.…”

A Four-Cell-Senescence-Regulator-Gene Prognostic Index Verified by Genome-Wide CRISPR Can Depict the Tumor Microenvironment and Guide Clinical Treatment of Bladder Cancer

“…PSMD14 is a kind of deubiquitinating enzymes (DUBs) and was reported to be connected with tumor progression and poor prognosis in many types of cancer including neck squamous cell carcinoma ( 38 ), non-small cell lung cancer ( 39 ), ovarian cancer ( 40 ), and hepatocellular carcinoma ( 41 ). Gong considered that a high expression of PSMD14 in tumor cells may lead to aging or failure of CD8+ T cells, which may explain the positive correlation between high expression of CD8+ T cells and PSMD14 and poor prognosis in osteosarcoma ( 42 ). PSMB5 is a member of the PSMB family and ubiquitin-proteasome system, which was demonstrated to play important roles in tumor progression and immune cell infiltration, especially in breast cancer.…”