Landscape of mitochondria genome and clinical outcomes in stage 1 lung adenocarcinoma

Lovely Raghav, Ya Hsuan Chang, Yi Chiung Hsu, Yu Cheng Li, Chih Yi Chen, Tsung Ying Yang, Kun Chieh Chen, Kuo Hsuan Hsu, Jeng Sen Tseng, Cheng Yen Chuang, Mei Hsuan Lee, Chih Liang Wang, Huei Wen Chen, Sung Liang Yu, Sheng Fang Su, Shin Sheng Yuan, Jeremy J.W. Chen, Shinn Ying Ho, Ker Chau Li, Pan Chyr YangGee Chen Chang, Hsuan Yu Chen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish
Article number755
JournalCancers
Volume12
Issue number3
DOIs
StatePublished - Mar 2020

Keywords

  • EGFR-activating mutations
  • Lung adenocarcinoma
  • Mitochondria
  • Prognosis
  • Somatic mutations

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