An integrative analysis reveals the prognostic value and potential functions of PSMD11 in hepatocellular carcinoma
An integrative analysis reveals the prognostic value and potential functions of PSMD11 in hepatocellular carcinoma
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DOI：
10.1002/mc.23568
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发表时间：
2023-05
影响因子：
4.6
通讯作者：
Cong Zhang;Tiantian Xu;Kun Ji;S. Cao;Yunbo Cao;Jing Ai;Li Jing;Junhui Sun
中科院分区：
文献类型：
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作者：
Cong Zhang;Tiantian Xu;Kun Ji;S. Cao;Yunbo Cao;Jing Ai;Li Jing;Junhui Sun
肝细胞癌（HCC）作为癌症相关死亡的一个重要病因，其全球负担表明迫切需要更深入地理解其基本生物学机制。在这种情况下，26S 蛋白酶体非 ATP 酶调节亚基 11 (PSMD11) 在 HCC 中的确切功能仍然模棱两可。为了解决这一重要的知识差距，我们查阅了癌症基因组图谱、基因型组织表达、国际癌症基因组联盟、基因表达综合、癌细胞系百科全书和肿瘤免疫单细胞中心数据库，以评估 PSMD11 的表达模式，并通过 LO2 中的逆转录定量聚合酶链反应 (RT-qPCR) 进一步证实， MHCC-97H、HepG2 和 SMMC7721 细胞系。此外，我们仔细评估了 PSMD11 的临床意义和预后价值，同时还探索了其在 HCC 中的潜在分子机制。我们的研究结果表明，PSMD11 在 HCC 组织中高表达，与病理分期和组织学分级相关，从而导致预后不良。从机制上讲，PSMD11似乎通过调节肿瘤代谢相关途径发挥其致瘤作用。令人印象深刻的是，低 PSMD11 表达与免疫效应细胞浸润增加、对达沙替尼、厄洛替尼、吉非替尼和伊马替尼等分子靶向药物的反应性增强以及体细胞突变率降低相关。此外，我们证明 PSMD11 可能通过与铜凋亡相关基因 ATP7A、DLAT 和 PDHA1 的复杂相互作用来调节 HCC 的发展。我们的综合分析表明 PSMD11 是 HCC 的一个有前途的治疗靶点。
The global burden of hepatocellular carcinoma (HCC) as a preeminent etiology of cancer‐related mortalities sheds light on the imperative necessity for a more profound comprehension of its fundamental biological mechanisms. In this context, the precise function of the 26S proteasome non‐ATPase regulatory subunit 11 (PSMD11) in HCC remains equivocal. To address this vital knowledge gap, we interrogated the cancer genome atlas, genotype‐tissue expression, International cancer genome consortium, gene expression omnibus, the cancer cell line encyclopedia, and tumor immune single‐cell hub databases to evaluate the expression pattern of PSMD11, further confirmed by reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) in LO2, MHCC‐97H, HepG2, and SMMC7721 cell lines. Additionally, we meticulously assessed the clinical significance and prognostic value of PSMD11, while also exploring its potential molecular mechanisms in HCC. Our findings demonstrated that PSMD11 was highly expressed in HCC tissues, correlating with pathologic stage and histologic grade, thereby conferring a poor prognosis. Mechanistically, PSMD11 appears to exert its tumorigenic effects through the modulation of tumor metabolism‐related pathways. Impressively, low PSMD11 expression was associated with increased immune effector cell infiltration, heightened responsiveness to molecular targeted drugs such as dasatinib, erlotinib, gefitinib, and imatinib, as well as reduced somatic mutation rate. Additionally, we demonstrated that PSMD11 might modulate HCC development through intricate interactions with cuproptosis‐related genes ATP7A, DLAT, and PDHA1. Our comprehensive analyses collectively suggest that PSMD11 represents a promising therapeutic target in HCC.