Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer
Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer
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DOI：
10.21873/anticanres.14035
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发表时间：
2020-02
影响因子：
2
通讯作者：
Takayuki Nakano;T. Go;N. Nakashima;Dage Liu;H. Yokomise
中科院分区：
文献类型：
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作者：
Takayuki Nakano;T. Go;N. Nakashima;Dage Liu;H. Yokomise
背景/目的：髓样细胞白血病-1（MCL-1）是B细胞淋巴瘤-2（Bcl-2）蛋白家族的成员，其调节内在（线粒体）凋亡级联反应。MCL-1抑制细胞凋亡，这可能与对癌症治疗的抗性有关。因此，本研究探讨MCL-1在非小细胞肺癌（NSCLC）中的临床作用。患者和方法：这项回顾性研究纳入了80例1-3A期NSCLC患者，这些患者在2010年至2011年期间接受了手术，未接受术前治疗。免疫组化法检测MCL-1表达和Ki-67指数。通过末端脱氧核苷酸转移酶dUTP缺口末端标记法测定细胞凋亡指数（AI）。结果如下：受试者工作特征曲线分析（曲线下面积=0.6785）显示，MCL-1在30.0%的NSCLC肿瘤细胞中的表达是预测预后的显著截止值。如果在>30%的细胞中观察到染色，则认为肿瘤是MCL-1阳性的。MCL-1阳性36例（45.0%）。然而，MCL-1表达与临床变量之间无显著差异。MCL-1阳性肿瘤的AI（2.2±3.6%）低于MCL-1阴性肿瘤（5.2±7.9%），但差异不显著（p=0.1080）。Ki-67指数在MCL-1阳性肿瘤中显著高于MCL-1阴性肿瘤（18.0% vs. 3.0%; p<0.001）。MCL-1阳性肿瘤患者的5年生存率（68.3%）显著低于MCL-1阴性肿瘤患者（93.1%，p=0.0057）。单变量[风险比（HR）=5.041，p=0.0013]和多变量分析显示，MCL-1表达是一个重要的预后因素（HR=3.983，p=0.0411）。结论：NSCLC细胞中MCL-1的表达与AI呈负相关，与Ki-67指数呈正相关。MCL-1可能作为一个潜在的预后生物标志物和一个新的治疗靶点在NSCLC。
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.