RRC ID 37591
著者 Uzawa K, Kasamatsu A, Baba T, Kimura Y, Nakashima D, Higo M, Sakamoto Y, Ogawara K, Shiiba M, Tanzawa H.
タイトル Quantitative detection of circulating tumor-derived mitochondrial NADH subunit variants as a potential prognostic biomarker for oral cancer.
ジャーナル Int J Oncol
Abstract Circulating tumor cells (CTCs) and/or their relating molecules are promising determinants during the course of cancer treatment, especially for post-therapeutic monitoring. We recently reported the clinical relevance of detecting circulating tumor-associated mutant mitochondrial DNAs (mut-mtDNAs) at three different regions including the displacement loop, 12S-rRNA and 16S-rRNA in oral squamous cell carcinomas (OSCCs). In the present study, to further investigate if the other mut-mtDNAs have novel efficiency for detecting potential tumoral micrometastasis, mut-mtDNAs on the ND2 and ND3 regions of the genome in 240 clinical samples from patients with OSCC were assessed in vitro and in vivo by quantitative real-time PCR combined with high-resolution melting curve analysis. Furthermore, the clinical relevance was evaluated by the area under the receiver operating characteristic curve (AUC) analysis. Three discrete sequence variations were identified in OSCC derived cell lines at the regions of ND2 (T:A to C:G at position 5108) and ND3 (A:T to G:C at position 10397 and C:G to T:A at position 10400), whereas no mutation was observed in normal control human normal oral keratinocytes. In OSCC patients examined, the presence of mut-mtDNAs in serum during the postoperative period accurately predicted poor prognoses (ND2 AUC, 0.761; ND3 AUC, 0.704). The data presented here provide a novel approach for detecting the circulating mut-mtDNAs that are promising molecular markers for evaluating tumoral micrometastasis in OSCCs.
巻・号 47(3)
ページ 1077-83
公開日 2015-9-1
DOI 10.3892/ijo.2015.3083
PMID 26179426
MeSH Animals Area Under Curve Biomarkers, Tumor / blood Biomarkers, Tumor / genetics Carcinoma, Squamous Cell / enzymology Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / pathology* Cell Line, Tumor DNA, Mitochondrial / blood DNA, Mitochondrial / genetics Electron Transport Complex I / blood Electron Transport Complex I / genetics* Humans Mice Mouth Neoplasms / enzymology Mouth Neoplasms / genetics Mouth Neoplasms / pathology* Mutation* NADH Dehydrogenase / blood NADH Dehydrogenase / genetics* Neoplasm Transplantation Neoplastic Cells, Circulating / metabolism* Prognosis
IF 3.899
引用数 6
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 HSC-4(RCB1902)