Zhao Haiyang, Luo Kexin, Liu Meihan, Cai Yuanze, Liu Siman, Li Shijuan, Zhao Yongsheng, Zhang Hongpan
Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
North Sichuan Medical College, Nanchong, China.
Front Genet. 2024 Oct 23;15:1458047. doi: 10.3389/fgene.2024.1458047. eCollection 2024.
Lung cancer is one of the most common malignant tumors, and patients are often diagnosed at an advanced stage, posing a substantial risk to human health, so it is crucial to establish a model to forecast the prognosis of patients with lung cancer. Recent research has indicated that proteasome 20S subunit 6 (PSMB6) may be closely associated with anti-apoptotic pathways, and proliferation transduction signals in tumor cells of different tumors. However, the precise role of PSMB6 in the immunoregulatory processes within lung adenocarcinoma (LUAD) is yet to be elucidated. By analyzing the TCGA database, we discovered a positive correlation between the expression of PSMB6 and tumor growth trends, and lung adenocarcinoma patients with elevated PSMB6 expression levels had a worse prognosis. Our findings suggest a close correlation between PSMB6 expression levels, immune cell infiltration and immune checkpoint gene expression, which suggests that PSMB6 may become a new independent prognostic indicator. In addition, we developed a prognostic model of PSMB6-regulated immune infiltration-associated genes by analyzing the link between PSMB6 and the immune microenvironment. This model can not only predict the prognosis of lung adenocarcinoma but also forecasts the patient's reaction to immunotherapy. The validity of this research outcome has been confirmed by the GSE31210 and IMvigor210 cohorts. Analysis of the Kaplan-Meier Plotter database indicates that individuals with elevated levels of PSMB6 expression exhibit a poorer prognosis. Additionally, experiments demonstrated that knockdown of PSMB6 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells while promoting their apoptosis. Overall, our findings suggest that PSMB6 could remarkably influence the management and treatment of lung adenocarcinoma, opening new avenues for targeted immunotherapeutic strategies.
肺癌是最常见的恶性肿瘤之一，患者常被诊断为晚期，对人类健康构成重大风险，因此建立一个预测肺癌患者预后的模型至关重要。最近的研究表明，蛋白酶体20S亚基6（PSMB6）可能与不同肿瘤的肿瘤细胞中的抗凋亡途径和增殖转导信号密切相关。然而，PSMB6在肺腺癌（LUAD）免疫调节过程中的确切作用尚待阐明。通过分析TCGA数据库，我们发现PSMB6的表达与肿瘤生长趋势呈正相关，且PSMB6表达水平升高的肺腺癌患者预后较差。我们的研究结果表明PSMB6表达水平、免疫细胞浸润和免疫检查点基因表达之间存在密切相关性，这表明PSMB6可能成为一个新的独立预后指标。此外，我们通过分析PSMB6与免疫微环境之间的联系，建立了一个由PSMB6调节的免疫浸润相关基因的预后模型。该模型不仅可以预测肺腺癌的预后，还可以预测患者对免疫治疗的反应。GSE31210和IMvigor210队列证实了这一研究结果的有效性。对Kaplan-Meier Plotter数据库的分析表明，PSMB6表达水平升高的个体预后较差。此外，实验表明，敲低PSMB6可抑制肺腺癌细胞的增殖、迁移和侵袭，同时促进其凋亡。总体而言，我们的研究结果表明，PSMB6可能对肺腺癌的管理和治疗产生显著影响，为靶向免疫治疗策略开辟了新途径。
