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

1
Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics-Polish Academy of Sciences, 02-106 Warsaw, Poland
2
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
3
Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
4
Department of Molecular Diagnostics, Holycross Cancer Center, 25-734 Kielce, Poland
5
Division of Medical Biology, Institute of Biology, Jan Kochanowski University, 25-369 Kielce, Poland
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Department of Gynecology, Holy Family Hospital, 02-544 Warsaw, Poland
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Department of Gynecologic Oncology, Holycross Cancer Center, 25-734 Kielce, Poland
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Chair and Department of Obstetrics, Gynecology and Oncology, 2nd Faculty of Medicine, Warsaw Medical University, 03-242 Warsaw, Poland
9
Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
10
Genomics Core Facility, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland
11
Department of Immunology, Biochemistry and Nutrition, Centre for Preclinical Research and Technologies, Medical University of Warsaw, 02-097 Warsaw, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2021, 13(1), 27; https://doi.org/10.3390/cancers13010027
Received: 10 November 2020 / Revised: 17 December 2020 / Accepted: 18 December 2020 / Published: 23 December 2020
Our study aimed to advance the understanding of vulvar squamous cell carcinoma (VSCC) biology by recognizing biological pathways that drive the progression of this disease. We applied the experimental path from global proteomic analysis of vulvar tumors to the targeted and quantitative assessment of specific proteins both in the tumors and blood of VSCC patients. The proteomic analysis has advanced the knowledge on VSCC biology by pointing at inflammation as a driver of progression and by providing grounds for the hypothesis of vulvovaginal microflora disturbances as a trigger for the inflammatory response. The study results indicate prognostic protein markers and potential therapeutic targets for improved and personalized management of VSCC.
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. View Full-Text
Keywords: HMGA2; iTRAQ; microbiome; proteomics; PRTN3; vulvar carcinoma HMGA2; iTRAQ; microbiome; proteomics; PRTN3; vulvar carcinoma
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MDPI and ACS Style

Fatalska, A.; Rusetska, N.; Bakuła-Zalewska, E.; Kowalik, A.; Zięba, S.; Wroblewska, A.; Zalewski, K.; Goryca, K.; Domański, D.; Kowalewska, M. Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression. Cancers 2021, 13, 27. https://doi.org/10.3390/cancers13010027

AMA Style

Fatalska A, Rusetska N, Bakuła-Zalewska E, Kowalik A, Zięba S, Wroblewska A, Zalewski K, Goryca K, Domański D, Kowalewska M. Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression. Cancers. 2021; 13(1):27. https://doi.org/10.3390/cancers13010027

Chicago/Turabian Style

Fatalska, Agnieszka, Natalia Rusetska, Elwira Bakuła-Zalewska, Artur Kowalik, Sebastian Zięba, Agnieszka Wroblewska, Kamil Zalewski, Krzysztof Goryca, Dominik Domański, and Magdalena Kowalewska. 2021. "Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression" Cancers 13, no. 1: 27. https://doi.org/10.3390/cancers13010027

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