Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis

Shatavisha Dasgupta; Patricia C Ewing-Graham; Thierry P P Van Den Bosch; Sigrid M A Swagemakers; Lindy A M Santegoets; Helena C Van Doorn; Peter J Van Der Spek; Senada Koljenović; Folkert J Van Kemenade

doi:10.3892/ol.2021.12642

Nuclear factor IB is downregulated in vulvar squamous cell carcinoma (VSCC): Unravelling differentially expressed genes in VSCC through gene expression dataset analysis

Oncol Lett. 2021 May;21(5):381. doi: 10.3892/ol.2021.12642. Epub 2021 Mar 16.

Affiliations

¹ Department of Pathology, Erasmus MC, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands.
² Department of Clinical Bioinformatics, Erasmus MC, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands.
³ Department of Obstetrics and Gynecology, Reinier de Graaf Gasthuis, 2625 AD Delft, The Netherlands.
⁴ Department of Gynecologic Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands.

Abstract

Vulvar squamous cell carcinoma (VSCC) comprises two distinct etiopathological subtypes: i) Human papilloma virus (HPV)-related VSCC, which arises via the precursor high grade squamous intraepithelial lesion (HSIL); and ii) HPV-independent VSCC, which arises via precursor, differentiated vulvar intraepithelial neoplasia (dVIN), driven by TP53 mutations. However, the mechanism of carcinogenesis of VSCC is poorly understood. The current study aimed to gain insight into VSCC carcinogenesis by identifying differentially expressed genes (DEGs) for each VSCC subtype. The expression of certain DEGs was then further assessed by performing immunohistochemistry (IHC) on whole tissue sections of VSCC and its precursors. Statistical analysis of microarrays was performed on two independent gene expression datasets (GSE38228 and a study from Erasmus MC) on VSCC and normal vulva. DEGs were identified that were similarly (up/down) regulated with statistical significance in both datasets. For HPV-related VSCCs, this constituted 88 DEGs, and for HPV-independent VSCCs, this comprised 46 DEGs. IHC was performed on VSCC (n=11), dVIN (n=6), HSIL (n=6) and normal vulvar tissue (n=7) with i) signal transducer and activator of transcription 1 (STAT1; an upregulated DEGs); ii) nuclear factor IB (NFIB; a downregulated DEG); iii) p16 (to determine the HPV status of tissues); and iv) p53 (to confirm the histological diagnoses). Strong and diffuse NFIB expression was observed in the basal and para-basal layers of normal vulvar tissue, whereas NFIB expression was minimal or completely negative in dVIN and in both subtypes of VSCC. In contrast, no discernable difference was observed in STAT1 expression among normal vulvar tissue, dVIN, HSIL or VSCC. By leveraging bioinformatics, the current study identified DEGs that can facilitate research into VSCC carcinogenesis. The results suggested that NFIB is downregulated in VSCC and its relevance as a diagnostic/prognostic biomarker deserves further exploration.

Keywords: bioinformatics; differentially expressed genes; female genital tract; gene expression omnibus database; gene expression profiling; immunohistochemistry; nuclear transcription factors; vulva.