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

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...

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Autores principales: Raghav, Lovely, Chang, Ya-Hsuan, Hsu, Yi-Chiung, Li, Yu-Cheng, Chen, Chih-Yi, Yang, Tsung-Ying, Chen, Kun-Chieh, Hsu, Kuo-Hsuan, Tseng, Jeng-Sen, Chuang, Cheng-Yen, Lee, Mei-Hsuan, Wang, Chih-Liang, Chen, Huei-Wen, Yu, Sung-Liang, Su, Sheng-Fang, Yuan, Shin-Sheng, Chen, Jeremy J.W., Ho, Shinn-Ying, Li, Ker-Chau, Yang, Pan-Chyr, Chang, Gee-Chen, Chen, Hsuan-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140061/
https://www.ncbi.nlm.nih.gov/pubmed/32210009
http://dx.doi.org/10.3390/cancers12030755
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author Raghav, Lovely
Chang, Ya-Hsuan
Hsu, Yi-Chiung
Li, Yu-Cheng
Chen, Chih-Yi
Yang, Tsung-Ying
Chen, Kun-Chieh
Hsu, Kuo-Hsuan
Tseng, Jeng-Sen
Chuang, Cheng-Yen
Lee, Mei-Hsuan
Wang, Chih-Liang
Chen, Huei-Wen
Yu, Sung-Liang
Su, Sheng-Fang
Yuan, Shin-Sheng
Chen, Jeremy J.W.
Ho, Shinn-Ying
Li, Ker-Chau
Yang, Pan-Chyr
Chang, Gee-Chen
Chen, Hsuan-Yu
author_facet Raghav, Lovely
Chang, Ya-Hsuan
Hsu, Yi-Chiung
Li, Yu-Cheng
Chen, Chih-Yi
Yang, Tsung-Ying
Chen, Kun-Chieh
Hsu, Kuo-Hsuan
Tseng, Jeng-Sen
Chuang, Cheng-Yen
Lee, Mei-Hsuan
Wang, Chih-Liang
Chen, Huei-Wen
Yu, Sung-Liang
Su, Sheng-Fang
Yuan, Shin-Sheng
Chen, Jeremy J.W.
Ho, Shinn-Ying
Li, Ker-Chau
Yang, Pan-Chyr
Chang, Gee-Chen
Chen, Hsuan-Yu
author_sort Raghav, Lovely
collection PubMed
description 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.
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spelling pubmed-71400612020-04-13 Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma Raghav, Lovely Chang, Ya-Hsuan Hsu, Yi-Chiung Li, Yu-Cheng Chen, Chih-Yi Yang, Tsung-Ying Chen, Kun-Chieh Hsu, Kuo-Hsuan Tseng, Jeng-Sen Chuang, Cheng-Yen Lee, Mei-Hsuan Wang, Chih-Liang Chen, Huei-Wen Yu, Sung-Liang Su, Sheng-Fang Yuan, Shin-Sheng Chen, Jeremy J.W. Ho, Shinn-Ying Li, Ker-Chau Yang, Pan-Chyr Chang, Gee-Chen Chen, Hsuan-Yu Cancers (Basel) Article 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. MDPI 2020-03-23 /pmc/articles/PMC7140061/ /pubmed/32210009 http://dx.doi.org/10.3390/cancers12030755 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Raghav, Lovely
Chang, Ya-Hsuan
Hsu, Yi-Chiung
Li, Yu-Cheng
Chen, Chih-Yi
Yang, Tsung-Ying
Chen, Kun-Chieh
Hsu, Kuo-Hsuan
Tseng, Jeng-Sen
Chuang, Cheng-Yen
Lee, Mei-Hsuan
Wang, Chih-Liang
Chen, Huei-Wen
Yu, Sung-Liang
Su, Sheng-Fang
Yuan, Shin-Sheng
Chen, Jeremy J.W.
Ho, Shinn-Ying
Li, Ker-Chau
Yang, Pan-Chyr
Chang, Gee-Chen
Chen, Hsuan-Yu
Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
title Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
title_full Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
title_fullStr Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
title_full_unstemmed Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
title_short Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma
title_sort landscape of mitochondria genome and clinical outcomes in stage 1 lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140061/
https://www.ncbi.nlm.nih.gov/pubmed/32210009
http://dx.doi.org/10.3390/cancers12030755
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