Table_1_C-Reactive Protein Levels Predict Responses to PD-1 Inhibitors in Hepatocellular Carcinoma Patients.docx

BackgroundSerum C-reactive protein (CRP) is a biomarker of an acute inflammatory response and has been successfully used as a prognostic predictor for several malignancies. However, the clinicopathological significance of CRP levels in hepatocellular carcinoma (HCC) patients being treated with PD-1 inhibitors remains unclear.
MethodsSerum CRP levels were measured for a total of 101 HCC patients that had been treated with PD-1 inhibitors from July 2018 to November 2019. The clinicopathological data was retrospectively analyzed to identify any clinical implications between CRP levels and responses to PD-1 inhibitors and patients’ progression-free survival (PFS).
ResultsThe median PFS was 8.87 months in the CRP-low subgroup and 3.67 months in the CRP-high subgroup (P = 0.009). Univariate and multivariate Cox regression analysis demonstrated that both serum CRP and AFP levels were independent risk factors for the PFS of HCC patients treated with PD-1 inhibitors (P < 0.05). Moreover, Cox regression analysis after Propensity Score Matching showed the similar results. A prognostic model combining CRP and AFP levels could significantly stratify HCC patients receiving PD-1 inhibitors into low-, intermediate-, and high-risk subgroups (P < 0.001). Patients in the risk subgroups reported similar overall response rates (P = 0.625) and significantly different disease control rates (low- vs. intermediate- vs. high-risk groups: 81.6% vs. 65.1% vs. 35%, respectively, P = 0.002).
ConclusionsThe results of this study support the association between high serum CRP levels with the response and PFS for HCC patients receiving PD-1 inhibitors. Furthermore, the levels of both CRP and AFP in an HCC patient before treatment initiation show great potential for determining the efficacy of PD-1 inhibitors.

背景
血清C反应蛋白（CRP）是急性炎症反应的生物标志物，已被成功用作多种恶性肿瘤的预后预测指标。然而，接受PD-1抑制剂治疗的肝细胞癌（HCC）患者中，CRP水平的临床病理意义仍不明确。
方法
本研究回顾性分析了2018年7月至2019年11月期间接受PD-1抑制剂治疗的101例肝细胞癌患者的血清CRP水平及临床病理资料，以探讨CRP水平与PD-1抑制剂治疗应答、患者无进展生存期（PFS）之间的临床关联。
结果
CRP低亚组患者的中位无进展生存期为8.87个月，CRP高亚组则为3.67个月（P=0.009）。单因素及多因素Cox回归分析显示，血清CRP与甲胎蛋白（AFP）水平均为接受PD-1抑制剂治疗的肝细胞癌患者无进展生存期的独立危险因素（P<0.05）。此外，倾向得分匹配（Propensity Score Matching, PSM）后的Cox回归分析得到了一致结果。联合CRP与AFP水平的预后模型可将接受PD-1抑制剂治疗的肝细胞癌患者显著划分为低、中、高三个风险亚组（P<0.001）。不同风险亚组患者的总体应答率相似（P=0.625），但疾病控制率存在显著差异：低、中、高风险组分别为81.6%、65.1%与35%（P=0.002）。
结论
本研究结果证实，血清CRP水平升高与接受PD-1抑制剂治疗的肝细胞癌患者的治疗应答及无进展生存期存在关联。此外，肝细胞癌患者治疗前的CRP与AFP水平，在预测PD-1抑制剂治疗疗效方面具有良好的临床应用潜力。