Saraswat Mayank, Mäkitie Antti, Agarwal Rahul, Joenväärä Sakari, Renkonen Suvi
Transplantation Laboratory, University of Helsinki, Haartmaninkatu 3, PO Box 21, Helsinki FI-00014, Finland.
HUSLAB, Helsinki University Hospital, Helsinki 00290, Finland.
Br J Cancer. 2017 Jul 25;117(3):376-384. doi: 10.1038/bjc.2017.172. Epub 2017 Jun 20.
No blood biomarkers to detect early oral cavity squamous cell carcinoma (OSCC) without clinical signs exist - diagnosis is solely based on histology of a visible tumour. Most OSCC patients are diagnosed at advanced stage, which leads to significant morbidity and poor survival. Our aim was to find the serum screening or detection biomarkers in OSCC.
Serum samples from patients with OSCC treated at the Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital (Finland) were collected. Age- and gender-matched healthy individuals served as controls. Quantitative label-free proteomics in high definition MS mode(HDMS) was performed on 13 patients and 12 healthy samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most influential proteins, which classify the patients vs healthy samples.
In quantitative proteomic analysis (HDMS), 388 proteins were quantified in our pilot study. A complete separation between cases and controls was seen in supervised and unsupervised classification techniques such as orthogonal projections on latent structure-discriminant analysis (OPLS-DA) and self-organising maps. Using OPLS-DA S-plot, we identified a set of eight proteins that completely separated OSCC patients from healthy individuals.
Although the tumour stages varied from I to IVa, these potential biomarkers were able to identify all OSCCs demonstrating their sensitivity to detect tumours of all stages. We are the first to suggest a set of serum biomarkers in our pilot study to be evaluated further as a diagnostic panel to detect preclinical OSCC in risk patients.
目前尚无用于在无临床症状时检测早期口腔鳞状细胞癌(OSCC)的血液生物标志物——诊断完全基于可见肿瘤的组织学检查。大多数OSCC患者在晚期才被诊断出来,这导致了严重的发病率和较差的生存率。我们的目的是寻找OSCC的血清筛查或检测生物标志物。
收集了在芬兰赫尔辛基大学医院耳鼻咽喉头颈外科接受治疗的OSCC患者的血清样本。年龄和性别匹配的健康个体作为对照。对13例患者样本和12例健康样本进行了高分辨率质谱模式(HDMS)下的无标记定量蛋白质组学分析。对定量蛋白质组学数据进行了各种统计分析,以获得最具影响力的蛋白质,从而对患者样本和健康样本进行分类。
在定量蛋白质组学分析(HDMS)中,我们的初步研究定量了388种蛋白质。在有监督和无监督的分类技术中,如潜在结构判别分析的正交投影(OPLS-DA)和自组织映射,病例组和对照组之间实现了完全分离。使用OPLS-DA S图,我们鉴定出一组8种蛋白质,它们能将OSCC患者与健康个体完全区分开。
尽管肿瘤分期从I期到IVa期各不相同,但这些潜在的生物标志物能够识别所有OSCC,表明它们对检测各阶段肿瘤具有敏感性。在我们的初步研究中,我们首次提出了一组血清生物标志物,有待进一步评估作为诊断组,用于检测高危患者的临床前OSCC。