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  • Title: 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.
    Author: Akamine T, Takada K, Toyokawa G, Kinoshita F, Matsubara T, Kozuma Y, Haratake N, Takamori S, Hirai F, Tagawa T, Okamoto T, Yoneshima Y, Okamoto I, Shimokawa M, Oda Y, Nakanishi Y, Maehara Y.
    Journal: Surg Oncol; 2018 Mar; 27(1):88-94. PubMed ID: 29549910.
    Abstract:
    OBJECTIVES: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic 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 platelet-lymphocyte 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.
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