Objective & method:
To identify protein expression differences between HPV+ and HPV- HNSCC in an open, unbiased approach we conducted a mass spectrometric comparison of a panel of HPV+ and HPV- OPSCC with similar characteristics as well as a comparison of HPV+ and HPV- HNSCC cell lines.
Results:
We identified a total of 2051 proteins from tumor tissues and a total of 3262 proteins from cell lines. As expected, the HPV surrogate marker p16 was identified to be expressed solely (tumors) or at a far higher level (cell lines) in HPV+ samples. A random forest analysis identified 24 proteins to be differentially expressed in tumor tissues with half of these proteins belonging to 3 functional groups: 1) Cytoskeletal regulators, 2) Replicative helicases and 3) Proteins of the nuclear envelope and lamina. Furthermore a component of various chromatin remodeling complexes and proposed radiosensitivity factor was expressed at a higher level in HPV+ tumors. Of note, only 2 of the 24 differentially expressed proteins were expressed at a higher level in HPV- tumors, among them a proposed stem cell factor with negative prognostic value in HNSCC. Preliminary analyses of the cell line comparison confirm some of results obtained with tumor samples but differed in others (e.g. replication factors).
Conclusions:
We identified differences between HPV+ and HPV- HNSCC, some of which will be further investigated for their mechanistic role and translational relevance as prognostic/predictive biomarkers, using in vitro studies and TMA analyses. The feasibility of cell culture models and the questions why and in which aspects they do or do not reflect tumor behavior and characteristics will also be further investigated.
