Zheng Hongmei, Ning Yue, Zhan Yuting, Liu Sile, Yang Yang, Wen Qiuyuan, Fan Songqing
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
J Cancer. 2021 Feb 2;12(7):2065-2072. doi: 10.7150/jca.53119. eCollection 2021.
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.
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。
