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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)88-94
Number of pages7
JournalSurgical Oncology
Volume27
Issue number1
DOIs
Publication statusPublished - Mar 1 2018

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Non-Small Cell Lung Carcinoma
C-Reactive Protein
Blood Proteins
Ligands
Lymphocytes
Smoking
Neutrophils
Biomarkers
History
Odds Ratio
ROC Curve
Immunotherapy
Blood Vessels
Monocytes
Proteins
Blood Platelets
Multivariate Analysis
Logistic Models

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

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. / 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.

In: Surgical Oncology, Vol. 27, No. 1, 01.03.2018, p. 88-94.

Research output: Contribution to journalArticle

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 2018, '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', Surgical Oncology, vol. 27, no. 1, pp. 88-94. https://doi.org/10.1016/j.suronc.2018.01.002
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. / 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. In: Surgical Oncology. 2018 ; Vol. 27, No. 1. pp. 88-94.
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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.",
author = "Takaki Akamine and Kazuki Takada and Gouji Toyokawa and Fumihiko Kinoshita and Taichi Matsubara and Yuka Kozuma and Naoki Haratake and Shinkichi Takamori and Fumihiko Hirai and Tetsuzo Tagawa and Tatsuro Okamoto and Yasuto Yoneshima and Isamu Okamoto and Mototsugu Shimokawa and Yoshinao Oda and Yoichi Nakanishi and Yoshihiko Maehara",
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T2 - A comprehensive analysis of systemic inflammatory markers

AU - Akamine, Takaki

AU - Takada, Kazuki

AU - Toyokawa, Gouji

AU - Kinoshita, Fumihiko

AU - Matsubara, Taichi

AU - Kozuma, Yuka

AU - Haratake, Naoki

AU - Takamori, Shinkichi

AU - Hirai, Fumihiko

AU - Tagawa, Tetsuzo

AU - Okamoto, Tatsuro

AU - Yoneshima, Yasuto

AU - Okamoto, Isamu

AU - Shimokawa, Mototsugu

AU - Oda, Yoshinao

AU - Nakanishi, Yoichi

AU - Maehara, Yoshihiko

PY - 2018/3/1

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N2 - 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.

AB - 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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