Dong Chengyuan, Guo Yadong, Yang Yanrong, Ge Xin
Department of Clinical Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
School of Medicine, Anhui University of Science and Technology, Huainan, China.
Front Immunol. 2024 Jan 19;15:1295693. doi: 10.3389/fimmu.2024.1295693. eCollection 2024.
PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.
蛋白酶体激活因子3（PSME3）在肿瘤进展中发挥着重要作用。然而，PSME3在泛癌中的预后价值及其在肿瘤免疫中的作用仍不清楚。我们利用来自癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库的大量RNA测序数据进行了一项全面研究。我们的研究揭示了PSME3在多种癌症类型中的异常表达水平，并揭示了PSME3高表达与不良临床结果之间的相关性，尤其是在肝癌（LIHC）和肺腺癌（LUAD）等癌症中。功能富集分析突出了PSME3的多种生物学功能，包括其参与蛋白质降解、免疫反应和干细胞调节。此外，PSME3与肿瘤微环境中的免疫浸润和免疫细胞有关联，表明其在塑造癌症免疫格局中的潜在作用。该研究还揭示了PSME3与免疫检查点表达之间的联系，实验验证表明PSME3正向调节CD276。这表明PSME3可能是免疫治疗中的一个潜在治疗靶点。此外，我们预测了靶向PSME3的敏感药物。最后，我们在单因素Cox和多因素Cox回归分析中均证实PSME3是一个独立的预后因素。我们还对PSME3对肝癌细胞增殖和伤口愈合的影响进行了初步验证。总之，我们的研究揭示了PSME3在癌症生物学、免疫调节和临床结果中的多方面作用，为个性化癌症治疗策略和免疫治疗的发展提供了关键见解。
