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) |