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Open AccessArticle

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

1
Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan
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Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 30010, Taiwan
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Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei 11529, Taiwan
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Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 32001, Taiwan
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Institute of Medicine, Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
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Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
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Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan
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Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan
10
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
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Department of Thoracic Medicine, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan
12
Graduate Institute of Toxicology, National Taiwan University, Taipei 10617, Taiwan
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Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 10617, Taiwan
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Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 10055, Taiwan
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Department of Statistics, University of California Los Angeles, Los Angeles, CA 90095-1554, USA
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Center of Genomic Medicine, National Taiwan University, Taipei 10617, Taiwan
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Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
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Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung 40704, Taiwan
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Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
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College of Medicine, National Taiwan University, Taipei 10617, Taiwan
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College of Life Science, National Taiwan University, Taipei 10617, Taiwan
22
Ph.D. Program in Microbial Genomics, National Chung Hsing University, Taichung 402, Taiwan
*
Authors to whom correspondence should be addressed.
Senior author.
Cancers 2020, 12(3), 755; https://doi.org/10.3390/cancers12030755
Received: 23 February 2020 / Revised: 18 March 2020 / Accepted: 18 March 2020 / Published: 23 March 2020
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. View Full-Text
Keywords: mitochondria; lung adenocarcinoma; EGFR-activating mutations; somatic mutations; prognosis mitochondria; lung adenocarcinoma; EGFR-activating mutations; somatic mutations; prognosis
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MDPI and ACS Style

Raghav, L.; Chang, Y.-H.; Hsu, Y.-C.; Li, Y.-C.; Chen, C.-Y.; Yang, T.-Y.; Chen, K.-C.; Hsu, K.-H.; Tseng, J.-S.; Chuang, C.-Y.; Lee, M.-H.; Wang, C.-L.; Chen, H.-W.; Yu, S.-L.; Su, S.-F.; Yuan, S.-S.; Chen, J.J.; Ho, S.-Y.; Li, K.-C.; Yang, P.-C.; Chang, G.-C.; Chen, H.-Y. Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma. Cancers 2020, 12, 755.

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