Evaluating the Prognostic and Therapeutic Potentials of the Proteasome 26S Subunit, ATPase (PSMC) Family of Genes in Lung Adenocarcinoma: A Database Mining Approach

Md Asad Ullah; Nafisa Nawal Islam; Abu Tayab Moin; Su Hyun Park; Bonglee Kim

doi:10.3389/fgene.2022.935286

Evaluating the Prognostic and Therapeutic Potentials of the Proteasome 26S Subunit, ATPase (PSMC) Family of Genes in Lung Adenocarcinoma: A Database Mining Approach

Front Genet. 2022 Jul 22:13:935286. doi: 10.3389/fgene.2022.935286. eCollection 2022.

Authors

Md Asad Ullah¹, Nafisa Nawal Islam¹, Abu Tayab Moin², Su Hyun Park³, Bonglee Kim^{3

4}

Affiliations

¹ Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Jahangirnagar University, Dhaka, Bangladesh.
² Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chattogram, Bangladesh.
³ Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Korea.
⁴ Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Korea.

Abstract

This study explored the prognostic and therapeutic potentials of multiple Proteasome 26S Subunit, ATPase (PSMC) family of genes (PSMC1-5) in lung adenocarcinoma (LUAD) diagnosis and treatment. All the PSMCs were found to be differentially expressed (upregulated) at the mRNA and protein levels in LUAD tissues. The promoter and multiple coding regions of PSMCs were reported to be differentially and distinctly methylated, which may serve in the methylation-sensitive diagnosis of LUAD patients. Multiple somatic mutations (alteration frequency: 0.6-2%) were observed along the PSMC coding regions in LUAD tissues that could assist in the high-throughput screening of LUAD patients. A significant association between the PSMC overexpression and LUAD patients' poor overall and relapse-free survival (p < 0.05; HR: >1.3) and individual cancer stages (p < 0.001) was discovered, which justifies PSMCs as the ideal targets for LUAD diagnosis. Multiple immune cells and modulators (i.e., CD274 and IDO1) were found to be associated with the expression levels of PSMCs in LUAD tissues that could aid in formulating PSMC-based diagnostic measures and therapeutic interventions for LUAD. Functional enrichment analysis of neighbor genes of PSMCs in LUAD tissues revealed different genes (i.e., SLIRP, PSMA2, and NUDSF3) previously known to be involved in oncogenic processes and metastasis are co-expressed with PSMCs, which could also be investigated further. Overall, this study recommends that PSMCs and their transcriptional and translational products are potential candidates for LUAD diagnostic and therapeutic measure discovery.

Keywords: PSMCs; biomarker; diagnostic; lung cancer; therapeutic.