AUTHOR=Zhao Huihui , Lu Guojun 

TITLE=Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.905581

DOI=10.3389/fgene.2022.905581

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Although previous studies reported that 26S proteasome non-ATPase regulatory subunit 2 (<italic>PSMD2</italic>) is involved in many human cancers. However, its clinical significance and function in lung adenocarcinoma remain unclear. Here, we examined the prognostic and immunological role of <italic>PSMD2</italic> in lung adenocarcinoma.</p><p><bold>Methods:</bold> The Cancer Genome Atlas (TCGA) was conducted to analyze <italic>PSMD2</italic> expression and verified using UALCAN. PrognoScan and Kaplan-Meier curves were utilized to assess the effect of <italic>PSMD2</italic> on survival. cBioPortal database was conducted to identify the mutation characteristics of <italic>PSMD2</italic>. Functional enrichment was performed to determine <italic>PSMD2</italic>-related function. Cancer Single-cell State Atlas (CancerSEA) was used to explore the cancer functional status of <italic>PSMD2</italic> at single-cell resolution. <italic>PSMD2-</italic>related immune infiltration analysis was conducted. Tumor-Immune system interaction database (TISIDB) was performed to verify the correlation between <italic>PSMD2</italic> expression and tumor-infiltrating lymphocytes (TILs).</p><p><bold>Results:</bold> Both mRNA and protein expression of <italic>PSMD2</italic> were significantly elevated in lung adenocarcinoma. High expression of <italic>PSMD2</italic> was significantly correlated with high T stage (<italic>p</italic> = 0.014), lymph node metastases (<italic>p</italic> &lt; 0.001), and TNM stage <italic>p</italic> = 0.005). Kaplan-Meier curves indicated that high expression of <italic>PSMD2</italic> was correlated with poor overall survival (38.2 vs. 59.7 months, <italic>p</italic> &lt; 0.001) and disease-specific survival (59.9 months vs. not available, <italic>p</italic> = 0.004). Multivariate analysis suggested that <italic>PSMD2</italic> was an independent biomarker for poor overall survival (HR 1.471, 95%CI, 1.024–2.114, <italic>p</italic> = 0.037). <italic>PSMD2</italic> had a high mutation frequency of 14% in lung adenocarcinoma. The genetic mutation of <italic>PSMD2</italic> was also correlated with poor overall survival, disease-specific survival, and progression-free survival in lung adenocarcinoma. Functional enrichment suggested <italic>PSMD2</italic> expression was involved in the cell cycle, RNA transport, and cellular senescence. CancerSEA analysis indicated <italic>PSMD2</italic> expression was positively correlated with cell cycle, DNA damage, and DNA repair. Immune infiltration analysis suggested that <italic>PSMD2</italic> expression was correlated with immune cell infiltration levels and abundance of TILs.</p><p><bold>Conclusion:</bold> The upregulation of <italic>PSMD2</italic> is significantly correlated with poor prognosis and immune infiltration levels in lung adenocarcinoma. Our findings suggest that <italic>PSMD2</italic> is a potential biomarker for poor prognosis and immune therapeutic target in lung adenocarcinoma.</p>