Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer.
Anticancer Res
; 40(2): 1007-1014, 2020 Feb.
Article
en En
| MEDLINE
| ID: mdl-32014946
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 ANDMETHODS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
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Expresión Génica
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Carcinoma de Pulmón de Células no Pequeñas
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Proteína 1 de la Secuencia de Leucemia de Células Mieloides
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Neoplasias Pulmonares
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Anticancer Res
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón