Inflammation as a Driver of Vulvar Squamous Cell Carcinoma Progression.

Abstract

Background A knowledge on the biology of squamous cell vulvar carcinoma (VSCC) is limited. We aimed to identify protein markers of VSCC tumors stratifying patients by progression risk. Early stage VSCC tumors from patients who progressed (progVSCC) and from those who were disease-free (d-fVSCC) during follow-up, along with normal vulvar tissues were examined by mass spectrometry-based proteomics.Results In progVSCC vs d-fVSCC tumors, the immune response was the most over-represented Gene Ontology category for the identified DEPs. Interestingly, pathway profiling suggested bacterial infections to be linked to aggressive VSCC phenotypes. Differentially expressed proteins (DEPs) were verified in solid tissues and blood samples of patients with VSCC tumors and vulvar premalignant lesions. High Mobility Group AT-Hook 2 (HMGA2) and Proteinase 3 (PRTN3) were revealed as protein markers predicting VSCC progression.Conclusions HMGA2 and PRTN3 abundances are associated with aggressive VSCC phenotype, and hold promise as markers for patient stratification. It appears that vulvovaginal microflora disturbances trigger inflammatory response contributing to cancer progression.