Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: A comprehensive analysis of systemic inflammatory markers

作者：Akamine Takaki; Takada Kazuki; Toyokawa Gouji; Kinoshita Fumihiko; Matsubara Taichi; Kozuma Yuka; Haratake Naoki; Takamori Shinkichi; Hirai Fumihiko; Tagawa Tetsuzo; Okamoto Tatsuro; Yoneshima Yasuto; Okamoto Isamu; Shimokawa Mototsugu; Oda Yoshinao; Nakanishi Yoichi; Maehara Yoshihiko

来源：Surgical Oncology-Oxford, 2018, 27(1): 88-94.

DOI：10.1016/j.suronc.2018.01.002

• Programmed death-ligand 1
• C-reactive protein
• Non-small cell lung cancer

Objectives: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for m etastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients. Therefore, here we investigated the potential association of PD-L1 expression with systemic inflammatory markers, including CRP, NLR, lymphocyte-monocyte ratio and plateletlymphocyte ratio.
Methods: We retrospectively examined tumor PD-L1 expression in 508 surgically resected primary NSCLC cases by immunohistochemical analysis (cut-off value: 1%). The association of PD-L1 expression with preoperative systemic inflammatory markers was assessed by univariate and multivariate analyses. We generated a PD-L1 association score (A-score) from serum CRP level (cut-off value: 0.3 mg/dl) and smoking status to predict PD-L1 expression.
Results: Among the total 508 patients, 188 (37.0%) patients were positive for PD-L1 expression at the 1% cut-off value and 90 (17.5%) had elevated serum CRP level. Multivariate logistic regression revealed that PD-L1 positivity was significantly associated with advanced stage, the presence of vascular invasion and high serum CRP level (P =.0336,.0106 and 0.0018, respectively). Though not significant, smoking history tended to be associated with PD-L1 protein expression (P =.0717). There was no correlation with other inflammatory markers. Smoking history with elevated CRP level (A-score: 2) was strongly associated with PD-L1 protein expression (odds ratio: 5.18, P < .0001), while it was inversely associated with EGFR mutation (odds ratio: 0.11, P < .0001).
Conclusions: Our results indicate that among all systemic inflammatory markers examined, serum CRP seems to predict PD-L1 expression in patients with NSCLC however the clinical applicability is limited given the obtained area under the receiver operating characteristic curve values.

• 出版日期2018-3