Copy-number variation of MCL1 predicts overall survival of non-small-cell lung cancer in a Southern Chinese population.
BCL2L1 and MCL1 are key anti-apoptotic genes, and critical for cancer progression. The prognostic values of BCL2L1 and MCL1 copy-number variations (CNVs) in non-small-cell lung cancer (NSCLC) remain largely unknown. Somatic CNVs in BCL2L1 and MCL1 genes were tested in tumor tissues from 516 NSCLC patients in southern China; afterward, survival analyses were conducted with overall survival (OS) as outcome. Additionally, the associations between CNVs and mRNA expression levels were explored using data from 986 NSCLC patients in the Cancer Genome Atlas project. It was found that amplifications of BCL2L1 and MCL1 were associated with unfavorable OS of NSCLC, with adjusted hazards ratio of 1.62 (95% confident interval [CI] = 1.10-2.40; P = 0.015) and 1.39 (95% CI = 1.05-1.84; P = 0.020), respectively. Amplifications of MCL1, but not BCL2L1, were related with higher mRNA expression levels of corresponding gene, compared with non-amplifications (P = 0.005). Interestingly, after incorporating with MCL1 CNV status, clinical variables (age, sex, TNM stage, and surgical approach) showed an improved discriminatory ability to classify OS (area under curve increased from 72.2% to 74.1%; P = 0.042, DeLong's test). Overall, MCL1 CNV might be a prognostic biomarker for NSCLC, and additional investigations are needed to validate our findings.
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, 199 Ren-ai Road Industrial Park District, Suzhou, China.
Jieyun
J
Yin
Department of Thoracic Surgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Yangkai
Y
Li
Department of Social Science and Public Health, School of Basic Medical Science, Jiujiang University, No. 17, Lufeng Road, Jiujiang, 332000, China.
Hao
H
Zhao
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qin
Q
Qin
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiaorong
X
Li
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jiao
J
Huang
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yun
Y
Shi
Department of Thoracic Surgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Shufang
S
Gong
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Li
L
Liu
Department of Thoracic Surgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Xiangning
X
Fu
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shaofa
S
Nie
Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ws2008cn@gmail.com.
Sheng
S
Wei
D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D002681:China; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D009367:Neoplasm Staging; D011159:Population Surveillance; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors
C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein
BCL2L1; MCL1; copy-number variation; non-small-cell lung cancer; prognosis