Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma

Cancers

Pan-Chyr Yang¹  Yi-Chiung Hsu²  Sung-Liang Yu³  Chih-Liang Wang⁴  Kuo-Hsuan Hsu⁵  Kun-Chieh Chen⁵  Cheng-Yen Chuang⁶  Gee-Chen Chang⁷  Jeng-Sen Tseng⁷  Tsung-Ying Yang⁷  Sheng-Fang Su⁸  Huei-Wen Chen⁹  Shinn-Ying Ho^1,10  JeremyJ.W. Chen^1,11  Mei-Hsuan Lee^1,12  Chih-Yi Chen^1,13  Ker-Chau Li^1,14  Shin-Sheng Yuan^1,14  Ya-Hsuan Chang^1,14  Hsuan-Yu Chen^1,14  Lovely Raghav^1,14  Yu-Cheng Li^1,14 

[1] Center of Genomic Medicine, National Taiwan University, Taipei 10617, Taiwan;Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 32001, Taiwan;Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 10617, Taiwan;Department of Thoracic Medicine, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan;Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan;Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan;Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan;Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 10055, Taiwan;Graduate Institute of Toxicology, National Taiwan University, Taipei 10617, Taiwan;Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan;Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan;Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;Institute of Medicine, Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan;Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan;

关键词: mitochondria;    lung adenocarcinoma;    egfr-activating mutations;    somatic mutations;    prognosis;   

DOI  :  10.3390/cancers12030755

来源: DOAJ

【 摘 要 】

Risk factors including genetic effects are still being investigated in lung adenocarcinoma (LUAD). Mitochondria play an important role in controlling imperative cellular parameters, and anomalies in mitochondrial function might be crucial for cancer development. The mitochondrial genomic aberrations found in lung adenocarcinoma and their associations with cancer development and progression are not yet clearly characterized. Here, we identified a spectrum of mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with prognosis and clinical outcomes. Next-generation sequencing was used to reveal the mitochondrial genomes of tumor and conditionally normal adjacent tissues from 61 Stage 1 LUADs. Mitochondrial somatic mutations and clinical outcomes including relapse-free survival (RFS) were analyzed. Patients with somatic mutations in the D-loop region had longer RFS (adjusted hazard ratio, adjHR = 0.18, p = 0.027), whereas somatic mutations in mitochondrial Complex IV and Complex V genes were associated with shorter RFS (adjHR = 3.69, p = 0.012, and adjHR = 6.63, p = 0.002, respectively). The risk scores derived from mitochondrial somatic mutations were predictive of RFS (adjHR = 9.10, 95%CI: 2.93−28.32, p < 0.001). Our findings demonstrated the vulnerability of the mitochondrial genome to mutations and the potential prediction ability of somatic mutations. This research may contribute to improving molecular guidance for patient treatment in precision medicine.

【 授权许可】

Unknown