{"title":"Prognostic value and potential biological function of <i>PMSD11</i> in lung adenocarcinoma.","authors":"Yong Xi, Jing Zeng, Yundong Zhou, Weiyu Shen, Hirokazu Taniguchi, Retnagowri Rajandram, Sivakumar Krishnasamy","doi":"10.21037/jtd-24-1622","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The 26S non-ATPase regulatory subunit 11 (<i>PSMD11</i>) is a multiprotein complex that participates in the ATP-dependent degradation of ubiquitinated proteins and is essential to the regulation of embryonic stem cell proteasome activity. <i>PSMD11</i> has been demonstrated to be a factor contributing to the emergence and progression of cancer cells. However, the prognostic value and potential biological function of <i>PMSD11</i> in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to comprehensively investigate the prognostic and biological value of <i>PSMD11</i> in LUAD.</p><p><strong>Methods: </strong>We primarily endeavored to comprehensively investigate the prognostic and predictive value of <i>PSMD11</i> in patients with LUAD. Additionally, we aimed to further clarify the underlying mechanisms of <i>PSMD11</i> in LUAD tumorigenesis and progression via rigorous bioinformatics analyses, including expression analysis, survival analysis, clinicopathological analysis, immune microenvironment analysis, somatic mutation analysis, drug analysis, and cuproptosis analysis. Subsequently, we examined effect of <i>PSMD11</i> expression on immune escape in a non-small cell lung cancer (NSCLC) cell-T cell coculture model.</p><p><strong>Results: </strong>We found that <i>PSMD11</i> had a significantly higher expression in LUAD tissues than in normal lung tissues. Three clinical characteristics (age, stage, and overall survival event) exhibited significant differences between the <i>PSMD11</i> high- and low-expression groups. In biological function, <i>PSMD11</i> appears to exert its tumorigenic effects predominantly in pathways related to DNA replication and membrane-gated channel functions. Notably, we observed that <i>PSMD11</i> exhibited the strongest positive correlation with T helper 2 cells, gamma-delta T cells, and T regulatory cells and the highest negative correlation with B cells, mast cells, and CD8<sup>+</sup> T cells. Furthermore, we found that the expression of cuproptosis genes (<i>DLAT, DLD</i>, and <i>PDHA1</i>) was positively correlated with the expression of <i>PSMD11</i> (P<0.001).</p><p><strong>Conclusions: </strong>These results indicate that <i>PSMD11</i> has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.</p>","PeriodicalId":17542,"journal":{"name":"Journal of thoracic disease","volume":"16 11","pages":"7819-7835"},"PeriodicalIF":2.1000,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635249/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of thoracic disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/jtd-24-1622","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/29 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The 26S non-ATPase regulatory subunit 11 (PSMD11) is a multiprotein complex that participates in the ATP-dependent degradation of ubiquitinated proteins and is essential to the regulation of embryonic stem cell proteasome activity. PSMD11 has been demonstrated to be a factor contributing to the emergence and progression of cancer cells. However, the prognostic value and potential biological function of PMSD11 in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to comprehensively investigate the prognostic and biological value of PSMD11 in LUAD.
Methods: We primarily endeavored to comprehensively investigate the prognostic and predictive value of PSMD11 in patients with LUAD. Additionally, we aimed to further clarify the underlying mechanisms of PSMD11 in LUAD tumorigenesis and progression via rigorous bioinformatics analyses, including expression analysis, survival analysis, clinicopathological analysis, immune microenvironment analysis, somatic mutation analysis, drug analysis, and cuproptosis analysis. Subsequently, we examined effect of PSMD11 expression on immune escape in a non-small cell lung cancer (NSCLC) cell-T cell coculture model.
Results: We found that PSMD11 had a significantly higher expression in LUAD tissues than in normal lung tissues. Three clinical characteristics (age, stage, and overall survival event) exhibited significant differences between the PSMD11 high- and low-expression groups. In biological function, PSMD11 appears to exert its tumorigenic effects predominantly in pathways related to DNA replication and membrane-gated channel functions. Notably, we observed that PSMD11 exhibited the strongest positive correlation with T helper 2 cells, gamma-delta T cells, and T regulatory cells and the highest negative correlation with B cells, mast cells, and CD8+ T cells. Furthermore, we found that the expression of cuproptosis genes (DLAT, DLD, and PDHA1) was positively correlated with the expression of PSMD11 (P<0.001).
Conclusions: These results indicate that PSMD11 has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.
期刊介绍:
The Journal of Thoracic Disease (JTD, J Thorac Dis, pISSN: 2072-1439; eISSN: 2077-6624) was founded in Dec 2009, and indexed in PubMed in Dec 2011 and Science Citation Index SCI in Feb 2013. It is published quarterly (Dec 2009- Dec 2011), bimonthly (Jan 2012 - Dec 2013), monthly (Jan. 2014-) and openly distributed worldwide. JTD received its impact factor of 2.365 for the year 2016. JTD publishes manuscripts that describe new findings and provide current, practical information on the diagnosis and treatment of conditions related to thoracic disease. All the submission and reviewing are conducted electronically so that rapid review is assured.