Identification of hallmarks of lung adenocarcinoma prognosis using whole genome sequencing.
In conjunction with clinical characteristics, prognostic biomarkers are essential for choosing optimal therapies to lower the mortality of lung adenocarcinoma. Whole genome sequencing (WGS) of 7 cancerous-noncancerous tissue pairs was performed to explore the comparative copy number variations (CNVs) associated with lung adenocarcinoma. The frequencies of top ranked CNVs were verified in an independent set of 114 patients and then the roles of target CNVs in disease prognosis were assessed in 313 patients. The WGS yielded 2604 CNVs. After frequency validation and biological function screening of top 10 CNVs, 9 mutant driver genes from 7 CNVs were further analyzed for an association with survival. Compared with the PBXIP1 amplified copy number, unamplified carriers had a 0.62-fold (95%CI = 0.43-0.91) decreased risk of death. Compared with an amplified TERT, those with an unamplified TERT had a 35% reduction (95% CI = 3%-56%) in risk of lung adenocarcinoma progression. Cases with both unamplified PBXIP1 and TERT had a median 34.32-month extension of overall survival and 34.55-month delay in disease progression when compared with both amplified CNVs. This study demonstrates that CNVs of TERT and PBXIP1 have the potential to translate into the clinic and be used to improve outcomes for patients with this fatal disease.
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Li
L
Liu
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Jiao
J
Huang
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Ke
K
Wang
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Li
L
Li
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Yangkai
Y
Li
Department of Radiation Oncology, Center for Radiological Research, Columbia University Medical Center, New York, NY, USA.
Jingsong
J
Yuan
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Sheng
S
Wei
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D056970:Co-Repressor Proteins; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; C413449:PBXIP1 protein, human; D014157:Transcription Factors; C509186:TERT protein, human; D019098:Telomerase
copy number variation; lung adenocarcinoma; overall survival; progression free survival; whole genome sequencing