Luo Yulou, Ye Yinghui, Saibaidoula Yilina, Zhang Yuting, Chen Yan
Department of Breast Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
Department of Laboratory Medicine, Xinhua Hospital, Shenzhen, Guangdong Province, China.
PLoS One. 2025 May 7;20(5):e0323013. doi: 10.1371/journal.pone.0323013. eCollection 2025.
The Proteasome 20S subunit beta 8 (PSMB8) is an integral element of the immunoproteasome complex, playing a pivotal role in antigen processing. Despite its significance, the contributory role of PSMB8 in oncogenesis, particularly in thyroid carcinoma (THCA), has not been well-characterized. To address this gap in knowledge, our study endeavored to delineate the potential associations between PSMB8 and THCA. Transcriptomic profiles and clinical data of patients with THCA were retrieved from The Cancer Genome Atlas (TCGA) database to facilitate comprehensive analysis. Complementary resources from additional online databases were utilized to augment the study. Logistic regression analysis was employed to elucidate the relationship between PSMB8 and various clinicopathological parameters. Uni/multivariate Cox regression analyses were conducted to ascertain the independent prognostic factors for THCA patient outcomes. Quantitative polymerase chain reaction (qPCR) and western blot assays were employed to verify the expression level of PSMB8 in vitro. Our study demonstrated that PSMB8 was significantly upregulated in THCA, with its overexpression correlating with lymph node metastasis, extrathyroidal extension, and favorable prognosis. Immunohistochemistry substantiated a higher PSMB8 protein presence in THCA tissue compared to the normal, supporting its potential role as a moderately accurate diagnostic biomarker. Logistic regression analysis identified PSMB8 as a significant indicator of the N1 stage, classical histological subtype, and extrathyroidal extension. Age, T stage, and PSMB8 were further determined as independent prognostic factors for THCA. Functional investigations linked PSMB8 to immune processes, evidenced by its association with increased immune cell infiltration and higher stromal/immune scores, as well as a positive co-expression with several immune checkpoints. A constructed predicted competing endogenous RNA (ceRNA) network implicated PSMB8 in complex post-transcriptional regulation. Finally, in vitro assays confirmed the upregulation of PSMB8, underscoring its relevance in THCA and as a target for future research. Our work has preliminarily appraised PSMB8 as a biomarker with certain prognostic and diagnostic significance, and as a potential target for immunotherapy in THCA.
蛋白酶体20S亚基β8(PSMB8)是免疫蛋白酶体复合物的一个组成部分,在抗原加工中起关键作用。尽管其具有重要意义,但PSMB8在肿瘤发生中的作用,特别是在甲状腺癌(THCA)中的作用,尚未得到充分表征。为了填补这一知识空白,我们的研究致力于描绘PSMB8与THCA之间的潜在关联。从癌症基因组图谱(TCGA)数据库中检索THCA患者的转录组谱和临床数据,以促进全面分析。利用来自其他在线数据库的补充资源来加强该研究。采用逻辑回归分析来阐明PSMB8与各种临床病理参数之间的关系。进行单因素/多因素Cox回归分析,以确定THCA患者预后的独立预测因素。采用定量聚合酶链反应(qPCR)和蛋白质免疫印迹分析来验证体外PSMB8的表达水平。我们的研究表明,PSMB8在THCA中显著上调,其过表达与淋巴结转移、甲状腺外侵犯及良好预后相关。免疫组织化学证实,与正常组织相比,THCA组织中PSMB8蛋白含量更高,支持其作为中度准确诊断生物标志物的潜在作用。逻辑回归分析确定PSMB8是N1期、经典组织学亚型和甲状腺外侵犯的重要指标。年龄、T分期和PSMB8进一步被确定为THCA的独立预后因素。功能研究将PSMB8与免疫过程联系起来,证据是其与免疫细胞浸润增加和更高的基质/免疫评分相关,以及与多个免疫检查点的正共表达。构建的预测竞争性内源RNA(ceRNA)网络表明PSMB8参与复杂的转录后调控。最后,体外试验证实了PSMB8的上调,强调了其在THCA中的相关性以及作为未来研究靶点的地位。我们的工作初步评估了PSMB8作为具有一定预后和诊断意义的生物标志物,以及作为THCA免疫治疗潜在靶点的价值。