Csősz Éva, Márkus Bernadett, Darula Zsuzsanna, Medzihradszky Katalin F, Nemes Judit, Szabó Emese, Tőzsér József, Kiss Csongor, Márton Ildikó
Proteomics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine University of Debrecen Hungary.
Biomarker Research Group Department of Biochemistry and Molecular Biology Faculty of Medicine University of Debrecen Hungary.
FEBS Open Bio. 2018 Feb 19;8(4):556-569. doi: 10.1002/2211-5463.12391. eCollection 2018 Apr.
Oral squamous cell carcinoma (OSCC) is the seventh most common malignancy and the ninth most frequent cause of cancer death in Europe. Within Europe, Hungary has one of the highest rates of OSCC incidence and mortality. Thus, there is an urgent need to improve early detection. Saliva, as a readily available body fluid, became an increasingly important substance for the detection of biomarkers for many diseases. Different research groups have identified salivary biomarkers specific for OSCC for different countries. In this study, saliva samples of Hungarian patients with OSCC were studied to discover disease-specific and perhaps region-specific biomarkers. LC-mass spectrometry (MS)/MS analysis on a linear ion trap-Orbitrap mass spectrometer was used for qualitative and quantitative salivary protein profiling. More than 500 proteins were identified from saliva by shotgun proteomics. The up- and downregulated proteins in the saliva of patients with OSCC highlighted the importance of protein-protein interaction networks involving the immune system and proteolysis in disease development. Two potential biomarkers from our shotgun analysis and a third candidate reported earlier by a Taiwanese group were further examined by ELISA on a larger reference set of samples. Resistin, a biomarker reported in Taiwan but not validated in our study, highlights the necessity of application of standardized analysis methods in different ethnic or geographical populations to identify biomarkers with sufficient specificity and sensitivity.
口腔鳞状细胞癌(OSCC)是欧洲第七大常见恶性肿瘤,也是癌症死亡的第九大常见原因。在欧洲范围内,匈牙利的OSCC发病率和死亡率位居前列。因此,迫切需要改进早期检测方法。唾液作为一种易于获取的体液,对于许多疾病生物标志物的检测而言,其重要性日益凸显。不同的研究团队针对不同国家,已鉴定出OSCC特异性唾液生物标志物。在本研究中,对匈牙利OSCC患者的唾液样本进行了研究,以发现疾病特异性乃至可能的区域特异性生物标志物。利用线性离子阱-轨道阱质谱仪进行液相色谱-质谱联用(LC-MS)/MS分析,以对唾液蛋白质进行定性和定量分析。通过鸟枪法蛋白质组学从唾液中鉴定出500多种蛋白质。OSCC患者唾液中上调和下调的蛋白质突出了涉及免疫系统和蛋白水解的蛋白质-蛋白质相互作用网络在疾病发展中的重要性。通过酶联免疫吸附测定(ELISA),在更大的样本参考集中进一步检测了我们鸟枪法分析中的两种潜在生物标志物以及台湾一个团队先前报道的第三种候选生物标志物。抵抗素是台湾报道的一种生物标志物,但在我们的研究中未得到验证,这凸显了在不同种族或地理人群中应用标准化分析方法以鉴定具有足够特异性和敏感性的生物标志物的必要性。