1. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
2. Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
3. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
4. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science, Taipei Medical University, Taipei 11031, Taiwan.
5. Department of Statistics, Faculty of Science and Technology, PGRI Adi Buana University, East Java, Surabaya 60234, Indonesia.
6. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan.
The complexity of lung adenocarcinoma (LUAD) including many interacting biological processes makes it difficult to find therapeutic biomarkers for treatment. Previous studies demonstrated that PSMG (proteasome assembly chaperone) family members regulate the degradation of abnormal proteins. However, transcript expressions of this gene family in LUAD still need to be more fully investigated. Therefore, we used a holistic bioinformatics approach to explore PSMG genes involved in LUAD patients by integrating several high-throughput databases and tools including The Cancer Genome Atlas (TCGA), and Kaplan-Meier plotter database. These data demonstrated that PSMG3 and PSMG4 were expressed at significantly higher levels in neoplastic cells than in normal lung tissues. Notably, increased expressions of these proteins were correlated with poor prognoses of lung cancer patients, which probably confirmed their fundamental roles in the staging of LUAD tumors. Meanwhile, it was also indicated that there were positive correlations between PSMG family genes and the immune response, metabolism of ubiquinone, cell cycle regulatory pathways, and heat shock protein 90 (HSP90)/phosphatidylinositol 3-kinase (PI3K)/Wnt signaling. Experimental data also confirmed that the knockdown of PSMG4 in LUAD cell lines decreased cell proliferation and influenced expressions of downstream molecules. Collectively, this study revealed that PSMG family members are novel prognostic biomarkers for LUAD progression, which also provide new therapeutic targets of LUAD patients.
Keywords: PSMG family genes, Lung cancer, HSP90/PI3K/Wnt