Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28999
タイトル
Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer
ファイル
内容記述

Abstract

Background/aim: Myeloid cell leukemia-1 (MCL-1) is a member of the B-cell lymphoma-2 (Bcl-2) family of proteins, which regulate the intrinsic (mitochondrial) apoptotic cascade. MCL-1 inhibits apoptosis, which may be associated with resistance to cancer therapy. Therefore, in this study, the clinical role of MCL-1 in non-small cell lung cancer (NSCLC) was explored.

Patients and methods: This retrospective study included 80 patients with stage 1-3A NSCLC, who underwent surgery without preoperative treatment between 2010 and 2011. MCL-1 expression and Ki-67 index were determined via immunohistochemical staining. Apoptotic index (AI) was determined via terminal deoxynucleotidyl transferase dUTP nick end labeling.

Results: The receiver operating characteristic curve analysis (area under curve=0.6785) revealed that MCL-1 expression in 30.0% of the NSCLC tumor cells was a significant cut-off for predicting prognosis. Tumors were considered MCL-1-positive if staining was observed in >30% of the cells. Thirty-six tumors (45.0%) were MCL-1-positive. However, there were no significant differences between MCL-1 expression and clinical variables. AI was lower in MCL-1-positive (2.2±3.6%) than in MCL-1-negative (5.2±7.9%) tumors, although the difference was not significant (p=0.1080). The Ki-67 index was significantly higher in MCL-1-positive than in MCL-1-negative tumors (18.0% vs. 3.0%; p<0.001). Five-year survival rate was significantly worse in patients with MCL-1-positive tumors (68.3%) than in those with MCL-1-negative tumors (93.1%, p=0.0057). Univariate [hazard ratio (HR)=5.041, p=0.0013], and multivariate analyses revealed that MCL-1 expression was a significant prognostic factor (HR=3.983, p=0.0411).

Conclusion: MCL-1 expression in NSCLC cells correlated inversely with AI and positively with Ki-67 index. MCL-1 may serve as a potential prognostic biomarker and a novel therapeutic target in NSCLC.

Keywords:

Apoptosis; myeloid cell leukemia-1; non-small cell lung cancer; prognosis; survival

(医博甲749)

著者
著者 中野 貴之
著者(ヨミ) ナカノ タカユキ
著者(別表記) Nakano Takayuki
掲載誌
Anticancer Research
掲載誌(別表記)
Anticancer Res.
40
2
開始ページ
1007
終了ページ
1014
出版者
International Institute of Anticancer Research
出版年月日
2020-02
ISSN
0250-7005
NCID
AA10625860
PMID
32014946
DOI
10.21873/anticanres.14035
資料タイプ
学位論文
言語
英語
権利関係
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios)
"This is the Publisher's Version of the following article: Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer; Anticancer Research; Volume 40 Number 2 (2020) Pages: 1007-1014; doi:10.21873/anticanres.14035, which has been published in final form at https://doi.org/10.21873/anticanres.14035 . "
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博士論文(全文を含む)
学位授与番号
博甲第749号
学位授与年月日
2020-06-25
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.