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PD-L1与HIF-1α的共表达预示非小细胞肺癌患者术后预后不良。

Co-expression of PD-L1 and HIF-1α predicts poor prognosis in Patients with Non-small Cell Lung Cancer after surgery.

作者信息

Zheng Hongmei, Ning Yue, Zhan Yuting, Liu Sile, Yang Yang, Wen Qiuyuan, Fan Songqing

机构信息

Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

出版信息

J Cancer. 2021 Feb 2;12(7):2065-2072. doi: 10.7150/jca.53119. eCollection 2021.

Abstract

PD-L1 is highly expressed in multiple cancers and suppresses anticancer immunity. HIF-1α, as a vital transcription factor, could regulate the proliferation, metastasis, and apoptosis of cancer cells. The aim of this study was to explore the correlation between PD-L1 and HIF-1α protein and further estimate its clinicopathological/prognostic impact on NSCLC patients. In this study, expression of PD-L1 and HIF-1α protein was detected by immunohistochemistry in tissue microarrays of NSCLC and non-cancerous tissues. Expression of PD-L1 and HIF-1α protein was evidently elevated in NSCLC tissues compared with non-cancerous control lung tissues (both <0.05). Also, PD-L1 was higher in male, lung SCC patients with lymph node metastasis (all <0.05). There was a positive link between PD-L1 and HIF-1α in NSCLC (r=0.177, =0.005). What's more, overall survival of lung ADC patients had to do with PD-L1 and clinical stage, while that of SCC patients was related to HIF-1α, pathological grade and LNM status (all <0.05). Furthermore, multivariate analysis confirmed that PD-L1 and HIF-1α were considered to be independent prognostic factors for NSCLC patients (both <0.05). PD-L1 and HIF-1α may serve as attractive independent worse prognostic biomarkers for NSCLC patients and the combined evaluation of PD-L1 and HIF-1α may also be valuable for prognosis judgment. Additionally, expression of PD-L1 was positively correlated with HIF-1α, which may provide evidences for a novel combinational therapy targeting PD-L1 and HIF-1α in NSCLC patients.

摘要

程序性死亡配体1(PD-L1)在多种癌症中高表达,并抑制抗癌免疫。缺氧诱导因子-1α(HIF-1α)作为一种重要的转录因子,可调节癌细胞的增殖、转移和凋亡。本研究旨在探讨PD-L1与HIF-1α蛋白之间的相关性,并进一步评估其对非小细胞肺癌(NSCLC)患者的临床病理/预后影响。在本研究中,通过免疫组织化学检测NSCLC组织芯片和非癌组织中PD-L1和HIF-1α蛋白的表达。与非癌对照肺组织相比,NSCLC组织中PD-L1和HIF-1α蛋白的表达明显升高(均P<0.05)。此外,男性、有淋巴结转移的肺鳞癌患者的PD-L1表达更高(均P<0.05)。NSCLC中PD-L1与HIF-1α之间存在正相关(r=0.177,P=0.005)。此外,肺腺癌患者的总生存期与PD-L1和临床分期有关,而肺鳞癌患者的总生存期与HIF-1α、病理分级和淋巴结转移状态有关(均P<0.05)。此外,多因素分析证实,PD-L1和HIF-1α被认为是NSCLC患者的独立预后因素(均P<0.05)。PD-L1和HIF-1α可能是NSCLC患者有吸引力的独立不良预后生物标志物,联合评估PD-L1和HIF-1α对预后判断也可能有价值。此外,PD-L1的表达与HIF-1α呈正相关,这可能为NSCLC患者靶向PD-L1和HIF-1α的新型联合治疗提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ede4/7974520/f9153e3bb136/jcav12p2065g001.jpg

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