Jung Hae Il, Jeong Dongjun, Ji Sanghee, Ahn Tae Sung, Bae Sang Ho, Chin Susie, Chung Jun Chul, Kim Hyung Chul, Lee Moon Soo, Baek Moo-Jun
Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
Soonchunhyang Medical Science Research Institute, Soonchunhyang University College of Medicine, Cheonan, Korea.
Cancer Res Treat. 2017 Jan;49(1):246-254. doi: 10.4143/crt.2016.066. Epub 2016 Jul 7.
Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC.
Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis.
The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034).
The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.
肝细胞癌（HCC）是最具侵袭性的恶性肿瘤之一。最近，程序性细胞死亡蛋白1（PD-1）和PD-1配体1（PD-L1）的过表达已被证明与许多癌症的预后不良相关。然而，PD-L1或PD-1配体2（PD-L2）的表达与肝细胞癌临床结局尚未得到充分研究。
从85例行手术的肝细胞癌患者中获取福尔马林固定石蜡包埋样本。通过免疫组织化学分析评估PD-Ls（PD-L1、PD-L2）的表达。
PD-L1和PD-L2高表达组的比例分别为27.1%和23.5%。单因素分析显示，肿瘤大小（p<0.001）、组织学分化（p=0.010）、PD-L1表达（p<0.001）和PD-L2表达（p=0.039）是肝细胞癌患者总生存的显著预后因素。多因素分析显示，总体肿瘤大小（风险比[HR]，4.131；95%置信区间[CI]，2.233至7.643；p<0.001和HR，3.455；95%CI，1.967至6.067；p<0.001）和PD-L1表达（HR，5.172；95%CI，2.661至10.054；p<0.001和HR，3.730；95%CI，1.453至9.574；p=0.006）是总生存和无病生存的独立预后指标。PD-Ls高表达的患者生存率明显低于低表达患者（p<0.001，p=0.034）。
肝细胞癌患者中PD-Ls的过表达与生存及肿瘤复发相关。有必要进一步评估PD-1和PD-Ls作为肝细胞癌治疗靶点和预测生物标志物的价值。
