Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer 抗アポトーシス因子MCL-1の高発現は非小細胞肺癌患者の予後不良を予測する
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著者
書誌事項
- タイトル
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Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer
- タイトル別名
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抗アポトーシス因子MCL-1の高発現は非小細胞肺癌患者の予後不良を予測する
- 著者名
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中野, 貴之
- 学位授与大学
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香川大学
- 取得学位
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博士(医学)
- 学位授与番号
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甲第749号
- 学位授与年月日
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2020-06-25
注記・抄録
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.
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.