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鉴定和验证PSMB7作为肺腺癌预后和免疫浸润的新型生物标志物。

Identification and validation of PSMB7 as a novel biomarker for prognosis and immune infiltrates of lung adenocarcinoma.

作者信息

Chen Yan, Ran Xin, Fu Ping, Ao Jie, Zhu Guihua, Zhao Lianhua, Xiao HuaLiang

机构信息

Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China.

Department of Cancer Center, Daping Hospital, Army Medical University, Chongqing, China.

出版信息

PeerJ. 2025 Aug 29;13:e19958. doi: 10.7717/peerj.19958. eCollection 2025.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is one of the most prevalent types of lung cancer globally; it is characterized by high incidence and mortality rates and contributes to over 1.8 million deaths annually. PSMB7, a crucial component of the 20S proteasome involved in protein degradation and antigen presentation, has been implicated in various cancers; however, its specific function in LUAD remains inadequately explored.

METHODS

This research aimed to investigate the expression of PSMB7 in LUAD and its clinical significance using real-time quantitative PCR, immunohistochemistry, differential expression analysis, pathway enrichment analysis, immune cell infiltration, and DNA methylation.

RESULTS

PSMB7 expression levels in LUAD tissues were considerably higher than those in the surrounding normal lung tissues and were associated with advanced pathological stages and poorer clinical outcomes. High PSMB7 expression was correlated with reduced overall and disease-specific survival. Functional enrichment analysis indicated that the differentially expressed genes associated with PSMB7 were mainly involved in protein-DNA complex assembly and chromatin remodeling. Moreover, LUAD tissues showed lower DNA methylation in PSMB7 promoters than that in normal lung tissues, which was correlated with reduced survival rates. A negative correlation was observed between PSMB7 levels and immune cell infiltration, particularly for effector memory T, B, follicular helper T, and mast cells.

CONCLUSIONS

We identified PSMB7 as a promising biomarker for LUAD prognosis because of its strong association with tumor progression and immune microenvironment modulation. Future studies should explore therapeutic strategies targeting PSMB7 to improve patient outcomes for LUAD.

摘要

背景

肺腺癌(LUAD)是全球最常见的肺癌类型之一;其特点是发病率和死亡率高,每年导致超过180万人死亡。PSMB7是20S蛋白酶体的关键组成部分,参与蛋白质降解和抗原呈递,已被证明与多种癌症有关;然而,其在肺腺癌中的具体功能仍未得到充分探索。

方法

本研究旨在通过实时定量PCR、免疫组织化学、差异表达分析、通路富集分析、免疫细胞浸润和DNA甲基化来研究PSMB7在肺腺癌中的表达及其临床意义。

结果

肺腺癌组织中PSMB7的表达水平显著高于周围正常肺组织,并与晚期病理阶段和较差的临床结果相关。高PSMB7表达与总体生存率和疾病特异性生存率降低相关。功能富集分析表明,与PSMB7相关的差异表达基因主要参与蛋白质-DNA复合物组装和染色质重塑。此外,肺腺癌组织中PSMB7启动子的DNA甲基化水平低于正常肺组织,这与生存率降低相关。观察到PSMB7水平与免疫细胞浸润呈负相关,尤其是效应记忆T细胞、B细胞、滤泡辅助性T细胞和肥大细胞。

结论

我们确定PSMB7是肺腺癌预后的一个有前景的生物标志物,因为它与肿瘤进展和免疫微环境调节密切相关。未来的研究应探索针对PSMB7的治疗策略,以改善肺腺癌患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bae6/12401020/8f3af8fe888e/peerj-13-19958-g001.jpg

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