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首页> 外文期刊>International journal of oncology >Quantitative detection of circulating tumor-derived mitochondrial NADH subunit variants as a potential prognostic biomarker for oral cancer
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Quantitative detection of circulating tumor-derived mitochondrial NADH subunit variants as a potential prognostic biomarker for oral cancer

机译：定量检测循环肿瘤来源的线粒体NADH亚基变异体作为口腔癌潜在的预后生物标志物

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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.
机译：循环肿瘤细胞（CTC）和/或其相关分子是在癌症治疗过程中有希望的决定因素，尤其是在治疗后监测中。我们最近报道了在口腔鳞状细胞癌（OSCC）中检测包括循环环，12S-rRNA和16S-rRNA在内的三个不同区域的循环肿瘤相关突变线粒体DNA（mut-mtDNA）的临床意义。在本研究中，为进一步研究其他mut-mtDNA是否具有检测潜在的肿瘤微转移的新颖效率，在体外和体内对240例OSCC患者的临床样本中基因组ND2和ND3区的mut-mtDNA进行了评估。通过定量实时PCR与高分辨率熔解曲线分析相结合的方法。此外，通过接受者工作特征曲线（AUC）分析下的面积评估临床相关性。在OSCC衍生的细胞系中，在ND2（在5108位置的T：A至C：G）和ND3（在10397的A：T至G：C和在103：C：G至T：A）的区域中鉴定出三个离散的序列变异位置10400），而在正常对照人正常口腔角质形成细胞中未观察到突变。在接受检查的OSCC患者中，术后期间血清中mut-mtDNA的存在可准确预测不良预后（ND2 AUC，0.761; ND3 AUC，0.704）。此处提供的数据提供了一种检测循环mut-mtDNA的新颖方法，而mut-mtDNA是评估OSCC中肿瘤微转移的有前途的分子标记。

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