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

• Published in: Anticancer research 2020-02, Vol.40 (2), p.1007-1014
• Main Authors: Nakano, Takayuki, Go, Tetsuhiko, Nakashima, Nariyasu, Liu, Dage, Yokomise, Hiroyasu
• Format: Article
• Language: English
• Subjects: Adult; Aged; Apoptosis; Apoptosis - genetics; Bcl-2 protein; Biomarkers; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; DNA nucleotidylexotransferase; Female; Gene Expression; Humans; Leukemia; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lymphocytes B; Lymphoma; Male; Mcl-1 protein; Medical prognosis; Middle Aged; Mitochondria; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Non-small cell lung carcinoma; Patients; Prognosis; Proportional Hazards Models; ROC Curve; Small cell lung carcinoma; Staining; Surgery; Survival; Therapeutic applications; Tumor cells; Tumors
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14035

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. 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. 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