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泛素 C-末端水解酶-L1 在非小细胞肺癌中的表达及其与临床病理特征和预后的关系。

Ubiquitin C-terminal hydrolase-L1 expression in non-small-cell lung cancer and its association with clinicopathological features and prognosis.

机构信息

Department of Pathology, the Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin, 130041, China.

出版信息

Virchows Arch. 2022 Mar;480(3):577-585. doi: 10.1007/s00428-021-03199-y. Epub 2021 Nov 10.

DOI:10.1007/s00428-021-03199-y
PMID:34757486
Abstract

UbiquitinC-terminal hydrolase-L1 (UCH-L1) is a cysteine hydrolase. It functions as a ubiquitin hydrolase, stabilizes the ubiquitin monomer, and affects cell division through cell cycle protein deubiquitination. Abnormal UCH-L1 expression is closely related to the occurrence and development of several tumors. Although some in vitro studies have demonstrated the significance of UCH-L1 in non-small-cell lung cancer (NSCLC), only few clinical studies have focused on the UCH-L1 expression in NSCLC, and the results are controversial and non-uniform. We investigated the UCH-L1 expression in 401 cases of surgically resected NSCLC, including 286 cases of adenocarcinoma (ADC) and 65 cases of squamous cell carcinoma. The associations between the UCH-L1 expression and clinicopathological features, programmed cell death-ligand 1 (PD-L1) expression, and prognostic significance were analyzed. For NSCLC, the UCH-L1 expression is associated with sex, smoking history, tumor size (>3 cm), lymphocyte infiltration, advanced pathological stages, and shortened overall survival (OS; 89.72 vs. 114.55 months; P = 0.005), but not PD-L1 expression. The UCH-L1 expression in ADC is associated with advanced pathological stages, pleural invasion, and shortened OS (90.38 vs. 118.55 months; P = 0.010). Multivariate analysis confirmed that UCH-L1 expression was an independent poor prognostic factor for NSCLC (OS: hazard ratio [HR], 1.854; 95% confidence interval [CI], 1.132-3.038; P = 0.014). Our results suggest that the UCH-L1 expression differs across tumors with different clinicopathological features, and it is related to poor prognosis.

摘要

泛素 C 端水解酶-L1(UCH-L1)是一种半胱氨酸水解酶。它作为一种泛素水解酶发挥作用,稳定泛素单体,并通过细胞周期蛋白去泛素化影响细胞分裂。异常的 UCH-L1 表达与几种肿瘤的发生和发展密切相关。尽管一些体外研究表明 UCH-L1 在非小细胞肺癌(NSCLC)中的重要性,但只有少数临床研究关注 NSCLC 中的 UCH-L1 表达,结果存在争议且不一致。我们研究了 401 例手术切除的 NSCLC 中 UCH-L1 的表达,包括 286 例腺癌(ADC)和 65 例鳞状细胞癌。分析了 UCH-L1 表达与临床病理特征、程序性细胞死亡配体 1(PD-L1)表达和预后意义之间的关系。对于 NSCLC,UCH-L1 表达与性别、吸烟史、肿瘤大小(>3cm)、淋巴细胞浸润、晚期病理分期和总生存期(OS;89.72 与 114.55 个月;P=0.005)缩短相关,但与 PD-L1 表达无关。ADC 中的 UCH-L1 表达与晚期病理分期、胸膜侵犯和 OS 缩短(90.38 与 118.55 个月;P=0.010)相关。多变量分析证实 UCH-L1 表达是 NSCLC 的独立不良预后因素(OS:风险比[HR],1.854;95%置信区间[CI],1.132-3.038;P=0.014)。我们的结果表明,UCH-L1 表达在具有不同临床病理特征的肿瘤中存在差异,与预后不良相关。

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本文引用的文献

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Regulation and Function of the PD-L1 Checkpoint.PD-L1 检查点的调控与功能
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Cancer statistics in China, 2015.《中国癌症统计数据 2015》
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UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α.UCHL1因其对HIF-1α的去泛素化作用而提供了诊断和抗转移策略。
Nat Commun. 2015 Jan 23;6:6153. doi: 10.1038/ncomms7153.
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Potential prognostic marker ubiquitin carboxyl-terminal hydrolase-L1 does not predict patient survival in non-small cell lung carcinoma.潜在预后标志物泛素羧基末端水解酶-L1 不能预测非小细胞肺癌患者的生存。
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