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Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression.

Published version
Peer-reviewed

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Type

Article

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Authors

Fatalska, Agnieszka  ORCID logo  https://orcid.org/0000-0002-1720-4742
Rusetska, Natalia 
Bakuła-Zalewska, Elwira 
Zięba, Sebastian 

Abstract

Current knowledge on the biology of squamous cell vulvar carcinoma (VSCC) is limited. We aimed to identify protein markers of VSCC tumors that would permit to stratify patients by progression risk. Early-stage 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. Differentially expressed proteins (DEPs) were then verified in solid tissues and blood samples of patients with VSCC tumors and vulvar premalignant lesions. In progVSCC vs. d-fVSCC tumors, the immune response was the most over-represented Gene Ontology category for the identified DEPs. Pathway profiling suggested bacterial infections to be linked to aggressive VSCC phenotypes. High Mobility Group AT-Hook 2 (HMGA2) and Proteinase 3 (PRTN3) were revealed as proteins predicting VSCC progression. HMGA2 and PRTN3 abundances are associated with an aggressive phenotype, and hold promise as markers for VSCC patient stratification. It appears that vulvovaginal microflora disturbances trigger an inflammatory response contributing to cancer progression, suggesting that bacterial rather than viral infection status should be considered in the development of targeted therapies in VSCC.

Description

Keywords

HMGA2, PRTN3, iTRAQ, microbiome, proteomics, vulvar carcinoma

Journal Title

Cancers (Basel)

Conference Name

Journal ISSN

2072-6694
2072-6694

Volume Title

13

Publisher

MDPI AG