title: The opposite prognostic effect of NDUFS1 and NDUFS8 in lung cancer reflects the oncojanus role of mitochondrial complex I.
abstract: A recent surge of research on complex I mitochondrial DNA indicates that complex I disassembly regulated by mutation threshold plays a critical role in tumor progression. However, nuclear DNA (nDNA)-encoded core subunits are still a neglected area for cancer investigation. In this study, respective prognostic contributions of 7 nDNA-encoded core subunits were analyzed by immunohistochemical staining and RNA expression data extracted from public resources. The results showed that NDUFS1 and NDUFS8 had the most significant prognostic power in NSCLC patients among all 7 nDNA-encoded core subunits. Patients with low NDUFS1 or high NDUFS8 IHC and RNA expression levels had poor overall survival. Because of the significant correlation between expressions of 7 nDNA-encoded core subunits, multivariate analysis was performed and identified NDUFS1 and NDUFS8 IHC and RNA expression levels retained their leading prognostic roles. By combining NDFUS1 and NDUFS8 as a panel, the most unfavorable prognostic group had a 14-fold increased risk of poor prognosis than the most favorable prognostic group. In conclusion, the opposite prognostic effect of nDNA-encoded core subunits suggests the oncojanus role of nuclear genes regulating complex I dysfunction. The panel with NDUFS1 and NDUFS8 reflecting tumor metabolism status is a novel prognostic predictor for lung cancer.
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Chia-Yi
authors: CY
authors: Su
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Yu-Chan
authors: YC
authors: Chang
authors: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chih-Jen
authors: CJ
authors: Yang
authors: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Ming-Shyan
authors: MS
authors: Huang
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Michael
authors: M
authors: Hsiao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C487793:NDUFS1 protein, human; C113982:NDUFS8 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I