A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas

Gouji Toyokawa, Kazuki Takada, Tetsuzo Tagawa, Ryuji Hamamoto, Yuichi Yamada, Mototsugu Shimokawa, Yoshinao Oda, Yoshihiko Maehara

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Background: Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood. Methods: A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. Results: Among 428 patients, the EZH2 expression was identified in 219 (51.2%) patients, while the PD-L1 expression was observed in 88 (20.6%) patients. The recurrence-free and overall survival were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for recurrence-free and overall survival. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than did those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic and vessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70 years, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression. Conclusions: EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequently than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.

元の言語英語
ページ(範囲)393-400
ページ数8
ジャーナルAnnals of Thoracic Surgery
107
発行部数2
DOI
出版物ステータス出版済み - 2 1 2019

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Ligands
Adenocarcinoma of lung
Enhancer of Zeste Homolog 2 Protein
Recurrence
Lymphatic Vessels
Tumor Microenvironment
Survival
Epidermal Growth Factor Receptor
Epigenomics
Immunotherapy
Melanoma
Lung Neoplasms
Multivariate Analysis
Logistic Models
Immunohistochemistry
Regression Analysis
Genes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

これを引用

A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas. / Toyokawa, Gouji; Takada, Kazuki; Tagawa, Tetsuzo; Hamamoto, Ryuji; Yamada, Yuichi; Shimokawa, Mototsugu; Oda, Yoshinao; Maehara, Yoshihiko.

:: Annals of Thoracic Surgery, 巻 107, 番号 2, 01.02.2019, p. 393-400.

研究成果: ジャーナルへの寄稿記事

Toyokawa, Gouji ; Takada, Kazuki ; Tagawa, Tetsuzo ; Hamamoto, Ryuji ; Yamada, Yuichi ; Shimokawa, Mototsugu ; Oda, Yoshinao ; Maehara, Yoshihiko. / A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas. :: Annals of Thoracic Surgery. 2019 ; 巻 107, 番号 2. pp. 393-400.
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abstract = "Background: Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood. Methods: A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. Results: Among 428 patients, the EZH2 expression was identified in 219 (51.2{\%}) patients, while the PD-L1 expression was observed in 88 (20.6{\%}) patients. The recurrence-free and overall survival were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for recurrence-free and overall survival. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than did those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic and vessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70 years, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression. Conclusions: EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequently than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.",
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T1 - A Positive Correlation Between the EZH2 and PD-L1 Expression in Resected Lung Adenocarcinomas

AU - Toyokawa, Gouji

AU - Takada, Kazuki

AU - Tagawa, Tetsuzo

AU - Hamamoto, Ryuji

AU - Yamada, Yuichi

AU - Shimokawa, Mototsugu

AU - Oda, Yoshinao

AU - Maehara, Yoshihiko

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background: Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood. Methods: A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. Results: Among 428 patients, the EZH2 expression was identified in 219 (51.2%) patients, while the PD-L1 expression was observed in 88 (20.6%) patients. The recurrence-free and overall survival were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for recurrence-free and overall survival. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than did those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic and vessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70 years, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression. Conclusions: EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequently than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.

AB - Background: Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood. Methods: A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. Results: Among 428 patients, the EZH2 expression was identified in 219 (51.2%) patients, while the PD-L1 expression was observed in 88 (20.6%) patients. The recurrence-free and overall survival were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for recurrence-free and overall survival. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than did those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic and vessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70 years, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression. Conclusions: EZH2-expressing lung adenocarcinomas were shown to express the PD-L1 protein more frequently than were nonexpressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.

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