Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients

Shinkichi Takamori, Kazuki Takada, Koichi Azuma, Tomoko Jogo, Mototsugu Shimokawa, Gouji Toyokawa, Fumihiko Hirai, Tetsuzo Tagawa, Akihiko Kawahara, Jun Akiba, Isamu Okamoto, Yoichi Nakanishi, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. Methods: The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. Results: Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). Conclusions: The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.

Original languageEnglish
Pages (from-to)1916-1924
Number of pages9
JournalAnnals of Surgical Oncology
Volume26
Issue number6
DOIs
Publication statusPublished - Jun 15 2019

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Ligands
Adenocarcinoma of lung
Immunotherapy
Disease-Free Survival
Survival
Biomarkers
ROC Curve
Lung Neoplasms
Cell Death
Multivariate Analysis
Immunohistochemistry
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Takamori, S., Takada, K., Azuma, K., Jogo, T., Shimokawa, M., Toyokawa, G., ... Maehara, Y. (2019). Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients. Annals of Surgical Oncology, 26(6), 1916-1924. https://doi.org/10.1245/s10434-019-07231-z

Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients. / Takamori, Shinkichi; Takada, Kazuki; Azuma, Koichi; Jogo, Tomoko; Shimokawa, Mototsugu; Toyokawa, Gouji; Hirai, Fumihiko; Tagawa, Tetsuzo; Kawahara, Akihiko; Akiba, Jun; Okamoto, Isamu; Nakanishi, Yoichi; Oda, Yoshinao; Hoshino, Tomoaki; Maehara, Yoshihiko.

In: Annals of Surgical Oncology, Vol. 26, No. 6, 15.06.2019, p. 1916-1924.

Research output: Contribution to journalArticle

Takamori, S, Takada, K, Azuma, K, Jogo, T, Shimokawa, M, Toyokawa, G, Hirai, F, Tagawa, T, Kawahara, A, Akiba, J, Okamoto, I, Nakanishi, Y, Oda, Y, Hoshino, T & Maehara, Y 2019, 'Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients', Annals of Surgical Oncology, vol. 26, no. 6, pp. 1916-1924. https://doi.org/10.1245/s10434-019-07231-z
Takamori, Shinkichi ; Takada, Kazuki ; Azuma, Koichi ; Jogo, Tomoko ; Shimokawa, Mototsugu ; Toyokawa, Gouji ; Hirai, Fumihiko ; Tagawa, Tetsuzo ; Kawahara, Akihiko ; Akiba, Jun ; Okamoto, Isamu ; Nakanishi, Yoichi ; Oda, Yoshinao ; Hoshino, Tomoaki ; Maehara, Yoshihiko. / Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients. In: Annals of Surgical Oncology. 2019 ; Vol. 26, No. 6. pp. 1916-1924.
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abstract = "Background: Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. Methods: The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1{\%} according to a time-dependent receiver operating characteristic curve for 5-year survival. Results: Of the 433 patients, 306 (70.7{\%}) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). Conclusions: The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.",
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T1 - Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients

AU - Takamori, Shinkichi

AU - Takada, Kazuki

AU - Azuma, Koichi

AU - Jogo, Tomoko

AU - Shimokawa, Mototsugu

AU - Toyokawa, Gouji

AU - Hirai, Fumihiko

AU - Tagawa, Tetsuzo

AU - Kawahara, Akihiko

AU - Akiba, Jun

AU - Okamoto, Isamu

AU - Nakanishi, Yoichi

AU - Oda, Yoshinao

AU - Hoshino, Tomoaki

AU - Maehara, Yoshihiko

PY - 2019/6/15

Y1 - 2019/6/15

N2 - Background: Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. Methods: The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. Results: Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). Conclusions: The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.

AB - Background: Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. Methods: The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. Results: Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). Conclusions: The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.

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