Dai Xiaomeng, Pi Guoliang, Yang Sheng-Li, Chen George G, Liu Li-Ping, Dong Han-Hua
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430079, China.
Transl Oncol. 2018 Apr;11(2):559-566. doi: 10.1016/j.tranon.2018.02.014. Epub 2018 Mar 8.
To investigate the correlation between the expression of PD-L1 and HIF-1α in hepatocellular carcinoma (HCC) tissue and further analyze the association with clinical parameters and the prognostic value of coexpression in HCC patients.
We assessed the expression of PD-L1 and HIF-1α by immunohistochemistry in tumor tissue from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients.
PD-L1 and HIF-1α exhibited in tumor tissue high expression rates of 41.11% (37/90) and 43.33% (43/90), respectively, and their expressions were positively correlated (r = 0.563, P < .01). High expression of PD-L1 was significantly associated with low albumin levels (P < .05); high expression of HIF-1α was significantly correlated with high alpha-fetoprotein (AFP) levels and low albumin levels (P < .05); high expression of both PD-L1 and HIF-1α was also significantly associated with high AFP levels and low albumin levels (P < .05). High expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1 α was respectively significantly associated with worse overall survival (OS) and disease-free survival (DFS) (P < .05). Patients with co-overexpression of PD-L1 and HIF-1α had the worst prognosis compared with other groups. Additionally, multivariate Cox regression models suggested that high expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1α was an independent prognostic factor for OS and DFS (P < .05). Furthermore, the positive correlation and prognostic values of PD-L1 and HIF-1α were validated in an independent data set.
We demonstrated that HCC patients with co-overexpression of PD-L1 and HIF-1α in tumor tissue had a significantly higher risk of recurrence or metastasis and death compared with others. Therefore, more frequent follow-up is needed for patients with co-overexpression of PD-L1 and HIF-1α. At the same time, a combinational therapy with HIF-1α inhibitors in conjunction with PD-L1 blockade may be beneficial for HCC patients with co-overexpression in the future.
探讨肝细胞癌（HCC）组织中程序性死亡受体配体1（PD-L1）与缺氧诱导因子-1α（HIF-1α）表达的相关性，并进一步分析其与临床参数的关联以及共表达在HCC患者中的预后价值。
我们采用免疫组织化学法评估了90例行根治性肝切除术的HCC患者肿瘤组织中PD-L1和HIF-1α的表达。结果在另外90例HCC患者的独立队列中得到验证。
肿瘤组织中PD-L1和HIF-1α的高表达率分别为41.11%（37/90）和43.33%（43/90），且二者表达呈正相关（r = 0.563，P <.01）。PD-L1高表达与低白蛋白水平显著相关（P <.05）；HIF-1α高表达与高甲胎蛋白（AFP）水平和低白蛋白水平显著相关（P <.05）；PD-L1和HIF-1α均高表达也与高AFP水平和低白蛋白水平显著相关（P <.05）。PD-L1、HIF-1α以及PD-L1和HIF-1α均高表达分别与更差的总生存期（OS）和无病生存期（DFS）显著相关（P <.05）。与其他组相比，PD-L1和HIF-1α共过表达的患者预后最差。此外，多因素Cox回归模型表明，PD-L1、HIF-1α以及PD-L1和HIF-1α均高表达是OS和DFS的独立预后因素（P <.05）。此外，PD-L1和HIF-1α的正相关性和预后价值在独立数据集中得到验证结论：我们证明，肿瘤组织中PD-L1和HIF-1α共过表达的HCC患者与其他患者相比，复发或转移及死亡风险显著更高。因此，对于PD-L1和HIF-1α共过表达的患者需要更频繁的随访。同时，未来联合使用HIF-1α抑制剂与PD-L1阻断剂的联合治疗可能对共过表达的HCC患者有益。
