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用于口腔癌早期检测的潜在唾液mRNA生物标志物

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer.

作者信息

Oh Su Young, Kang Sung-Min, Kang Soo Hyun, Lee Heon-Jin, Kwon Tae-Geon, Kim Jin-Wook, Lee Sung-Tak, Choi So-Young, Hong Su-Hyung

机构信息

Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.

出版信息

J Clin Med. 2020 Jan 16;9(1):243. doi: 10.3390/jcm9010243.

Abstract

We evaluated potential biomarkers in human whole saliva for the early diagnosis of oral squamous cell carcinoma (OSCC). We selected 30 candidate genes with relevance to cancer from recent reports in PubMed. Saliva samples were obtained from 34 non-tumor control and 33 OSCC patients. Real-time PCR was performed, and mRNA levels were compared. Normalized mRNA levels of six genes (NGFI-A binding protein 2 (NAB2), cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1), nuclear pore complex interacting protein family, member B4 (NPIPB4), monoamine oxidase B (MAOB), sialic acid acetyltransferase (SIAE), and collagen, type III, alpha 1 (COL3A1)) were significantly lower in saliva of OSCC patients. Receiver operating characteristics (ROC) analysis was used to individually evaluate the predictive power of the potential biomarkers for OSCC diagnosis. The area under the curve (AUC) values were evaluated for the OSCC vs. non-tumor groups via univariate ROC analyses, as well as multivariate ROC analyses of combinations of multiple potential biomarkers. The combination of CYP27A1 + SIAE showed a favorable AUC value of 0.84. When we divided saliva samples into two groups according to age using a 60-year cut-off, with OSCC patients and controls evaluated together, the AUC of MAOB-NAB2 was more predictive of OSCC in the under-60 group (AUC, 0.91; sensitivity, 0.92; and specificity, 0.86) than any other gene combination. These results are expected to aid the early diagnosis of OSCC, especially in patients under 60 years of age. While more studies with larger numbers of patients are necessary, our result suggest that salivary mRNA would be a potent biomarker for early OSCC diagnosis.

摘要

我们评估了人类全唾液中的潜在生物标志物,用于口腔鳞状细胞癌(OSCC)的早期诊断。我们从PubMed最近的报告中选择了30个与癌症相关的候选基因。从34名非肿瘤对照者和33名OSCC患者中获取唾液样本。进行实时PCR,并比较mRNA水平。OSCC患者唾液中六个基因(NGFI-A结合蛋白2(NAB2)、细胞色素P450家族27亚家族A多肽1(CYP27A1)、核孔复合体相互作用蛋白家族成员B4(NPIPB4)、单胺氧化酶B(MAOB)、唾液酸乙酰转移酶(SIAE)和III型胶原蛋白α1(COL3A1))的标准化mRNA水平显著较低。采用受试者工作特征(ROC)分析单独评估潜在生物标志物对OSCC诊断的预测能力。通过单变量ROC分析以及多种潜在生物标志物组合的多变量ROC分析,评估OSCC组与非肿瘤组的曲线下面积(AUC)值。CYP27A1 + SIAE的组合显示出良好的AUC值,为0.84。当我们以60岁为界将唾液样本分为两组,同时评估OSCC患者和对照时,MAOB-NAB2的AUC在60岁以下组中对OSCC的预测性比任何其他基因组合都更高(AUC为0.91;敏感性为0.92;特异性为0.86)。这些结果有望有助于OSCC的早期诊断,尤其是60岁以下的患者。虽然需要更多对大量患者的研究,但我们结果表明唾液mRNA将是早期OSCC诊断的有力生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a83/7019677/7b7d7011f2d1/jcm-09-00243-g001.jpg

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