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

Raghav, Lovely; Hsu, Yi Chiung; Li, Yu Cheng; Chen, Chih Yi; Yang, Tsung Ying; Chen, Kun Chieh; Hsu, Kuo-Hsuan; Tseng, Jeng‐Sen; Chuang, Chun‐Yi; Lee, Hsuan-Shu; Wang, Chih Liang; Chen, Huei‐Wen; Yu, Sung-Liang; Su, Shih Bin; Yuan, Shin Sheng; Chen, Jeremy J.W.; Ho, Shinn-Ying; Li, Ker Chau; Yang, Pan Chyr; Chang, Gee Chen; Chen, Hsuan Yu

doi:10.3390/cancers12030755

Cited by 12 publications

(10 citation statements)

References 52 publications

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“…Mitochondrial biogenesis was higher in the ALT group than in the telomerase group according to a previous study [ 23 ]. The vulnerability of the mitochondrial genome to mutations and the somatic mutations promote poor prognosis [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Sung

Cheong

2021

IJMS

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Understanding the telomere maintenance mechanism (TMM) in immortal cancer cells is vital for TMM-targeted therapies in clinical settings. In this study, we classified four telomere maintenance mechanisms into telomerase, ALT, telomerase + ALT, and non-defined telomere maintenance mechanism (NDTMM) across 31 cancer types using 10,704 transcriptomic datasets from The Cancer Genome Atlas. Our results demonstrated that approximately 50% of the total cohort displayed ALT activity with high telomerase activity in most cancer types. We confirmed significant patient prognoses according to distinct TMMs in six cancer types: adrenocortical carcinoma (ACC), PAAD, HNSC, SARC, GBM, and metastatic cancer. Patients with metastasis had a poor prognosis in the ALT group (p < 0.006) subjected to RAS protein signal transduction. Glioblastoma patients had poor prognosis in NDTMM (p < 0.0043) and showed high levels of myeloid leukocyte activation. Pancreatic adenocarcinoma (p < 0.04) and head and neck squamous cell carcinoma (p < 0.046) patients had a good prognosis in the ALT group with high immune cell activation. Furthermore, we showed that master transcriptional regulators might affect the selection of the TMM pathway and explained why different telomere maintenance mechanisms exist. Furthermore, they can be used to segregate patients and predict responders to different TMM-targeted therapeutics.

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Section: Resultsmentioning

confidence: 99%

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Sung

Cheong

2021

IJMS

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“…Raghav et al found that the mean germline mtDNA mutation rate in stage 1 lung adenocarcinoma was 2.29 mutations per kbp. Most of the mutations occurred in the D-loop and the CYTB gene (which are part of the mitochondrial respiratory chain) [ 149 ].…”

Section: The Role Of Mitochondria and Mtdna In The Development Of Lun...mentioning

confidence: 99%

The Role of Mitochondrial miRNAs in the Development of Radon-Induced Lung Cancer

et al. 2022

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MicroRNAs are short, non-coding RNA molecules regulating gene expression by inhibiting the translation of messenger RNA (mRNA) or leading to degradation. The miRNAs are encoded in the nuclear genome and exported to the cytosol. However, miRNAs have been found in mitochondria and are probably derived from mitochondrial DNA. These miRNAs are able to directly regulate mitochondrial genes and mitochondrial activity. Mitochondrial dysfunction is the cause of many diseases, including cancer. In this review, we consider the role of mitochondrial miRNAs in the pathogenesis of lung cancer with particular reference to radon exposure.

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“…A study regarding mitochondria genome in stage I pulmonary adenocarcinoma showed that patients with somatic mutations in the D-loop region had longer relapse-free survival (RFS) than those without, whereas somatic mutations in mitochondrial Complex IV and Complex V genes were related to shorter RFS [87]. In pulmonary adenocarcinoma, the NGS study also showed six potential oncogenic genes, including AGR2, SPDEF, CDKN2A, CLDN3, SFN, and PHLDA2, and seven tumor suppressor genes [88].…”

Section: Rare Mutation Other Than Egfr and Alkmentioning

confidence: 99%

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Luo

Liang²,

Huang³

et al. 2022

IJMS

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Lung cancers are life-threatening malignancies that cause great healthcare burdens in Taiwan and worldwide. The 5-year survival rate for Taiwanese patients with lung cancer is approximately 29%, an unsatisfactorily low number that remains to be improved. We first reviewed the molecular epidemiology derived from a deep proteogenomic resource in Taiwan. The nuclear factor erythroid 2-related factor 2 (NRF2)antioxidant mechanism was discovered to mediate the oncogenesis and tumor progression of lung adenocarcinoma. Additionally, DNA replication, glycolysis and stress response are positively associated with tumor stages, while cell-to-cell communication, signaling, integrin, G protein coupled receptors, ion channels and adaptive immunity are negatively associated with tumor stages. Three patient subgroups were discovered based on the clustering analysis of protein abundance in tumors. The first subgroup is associated with more advanced cancer stages and visceral pleural invasion, as well as higher mutation burdens. The second subgroup is associated with EGFR L858R mutations. The third subgroup is associated with PI3K/AKT pathways and cell cycles. Both EGFR and PI3K/AKT signaling pathways have been shown to induce NRF2 activation and tumor cell proliferation. We also reviewed the clinical evidence of patient outcomes in Taiwan given various approved targeted therapies, such as EGFR-tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK)inhibitors, in accordance with the patients’ characteristics. Somatic mutations occurred in EGFR, KRAS, HER2 and BRAF genes, and these mutations have been detected in 55.7%, 5.2%, 2.0% and 0.7% patients, respectively. The EGFR mutation is the most prevalent targetable mutation in Taiwan. EML4-ALK translocations have been found in 9.8% of patients with wild-type EGFR. The molecular profiling of advanced NSCLC is critical to optimal therapeutic decision-making. The patient characteristics, such as mutation profiles, protein expression profiles, drug-resistance profiles, molecular oncogenic mechanisms and patient subgroup systems together offer new strategies for personalized treatments and patient care.

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

Cited by 12 publications

References 52 publications

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

The Role of Mitochondrial miRNAs in the Development of Radon-Induced Lung Cancer

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

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