C-Reactive Protein Levels Predict Responses to PD-1 Inhibitors in Hepatocellular Carcinoma Patients

• DOI: 10.3389/fimmu.2022.808101
• Publication Date: 2022-02-04T05:23:50Z
• Authors: Yiyang Zhang; Lianghe Lu; Zhangping He; Zhishen Xu; Zhicheng Xiang; Run-Cong Nie; Wenping Lin; Wenxu Chen; Jie Zhou; Yixin Yin; Juanjuan Xie; Youcheng Zhang; Xueyi Zheng; Tianchen Zhu; Xiaoxia Cai; Peng Li; Xue Chao; Mu-Yan Cai
• Keywords: Male; Carcinoma, Hepatocellular; Immunology; Disease-Free Survival; C-reactive protein; 03 medical and health sciences; 0302 clinical medicine; Predictive Value of Tests; Risk Factors; Biomarkers, Tumor; Humans; Immune Checkpoint Inhibitors; Retrospective Studies; tumor response; Liver Neoplasms; hepatocellular carcinoma; RC581-607; Middle Aged; Prognosis; 3. Good health; C-Reactive Protein; Multivariate Analysis; Female; PD-1 inhibitors; prognosis; alpha-Fetoproteins; Immunologic diseases. Allergy

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.