Patients with early-stage oropharyngeal cancer can be identified with label-free serum proteomics

利用无标记血清蛋白质组学可识别早期口咽癌患者

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作者:Anna Tuhkuri, Mayank Saraswat, Antti Mäkitie, Petri Mattila, Robert Silén, Amy Dickinson, Timo Carpén, Tiialotta Tohmola, Sakari Joenväärä, Suvi Renkonen

Background

The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is mainly related to human papillomavirus (HPV) infection. As OPSCCs are often diagnosed at an advanced stage, mortality and morbidity remain high. There are no diagnostic biomarkers for early detection of OPSCC.

Conclusions

We found a set of serum proteins distinguishing early-stage OPSCC from healthy individuals, and suggest a protein set for further evaluation as a diagnostic biomarker panel for OPSCC.

Methods

Serum from 25 patients with stage I-II OPSCC, and 12 healthy controls, was studied with quantitative label-free proteomics using ultra-definition MSE. Statistical analyses were performed to identify the proteins most reliably distinguishing early-stage OPSCCs from controls. P16 was used as a surrogate marker for HPV. P16-positive and P16-negative tumours were analysed separately.

Results

With two or more unique proteins per identification, 176 proteins were quantified. A clear separation between patients with early-stage tumours and controls was seen in principal component analysis. Latent structures discriminant analysis identified 96 proteins, most reliably differentiating OPSCC patients from controls, with 13 upregulated and 83 downregulated proteins in study cases. The set of proteins was studied further with network, pathway and protein-protein interaction analyses, and found to participate in lipid metabolism, for example. Conclusions: We found a set of serum proteins distinguishing early-stage OPSCC from healthy individuals, and suggest a protein set for further evaluation as a diagnostic biomarker panel for OPSCC.

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