Background: biomarkers useful for the identification of patients at risk of developing vulvar squamous cell carcinoma (VSCC) on a vulvar lichen sclerosus (VLS) background could lead to relevant prognostic advantages. To date, such biomarkers are not available. Objectives: we aimed to search for such biomarkers by evaluating the expression of microRNAs (miRNAs) in VLS samples that evolved or did not evolve into VSCCs. Methods: in this observational study, ten VLS samples that had not evolved into VSCC (VLS free from cancer, VLSfc) and 13 VLS samples that either had evolved into or were concomitant to high-risk HPV-negative VSCC (VLS cancer-associated, VLSca) were included. Total RNA, including miRNA, was isolated from formalin-fixed paraffin-embedded VLS samples. MiRNAseq analysis was employed to measure miRNA abundance. Differentially expressed miRNAs were identified using Qlucore Omics Explorer. To assess the risk prediction of each sample, the algorithm PAM (Prediction Analysis of Microarrays) was employed. The DIANA-mirPath database v.3 was used to identify biological pathways targeted by the differentially expressed microRNAs. Results: a smallRNA seq analysis conducted on 6 VLSca and 5 VLSfc samples revealed 163 differentially expressed miRNAs. By performing an independent smallRNA seq in a second set of samples (7 LVSca and 5 LVSfc) we assessed the capacity to discriminate between evolved and non-evolved VLS of a subpanel of 21 miRNAs. The results of PAM analysis showed that this set of 21 miRNAs correctly classified 19 out of the 23 samples (83%), with a probability close to 100% in most of the cases. The DIANA-mirPath database revealed the most significant pathways targeted by up- or down-regulated miRNAs, suggesting that a signature linked to cancer was already present in the VLSca samples. Conclusions: This study provided a strong indication that a selected subset of differentially expressed miRNAs exists between VLS that evolved and VLS that did not evolve towards cancer. MiRNA expression signature appears a potential early predictive biomarker of the risk of carcinogenesis in VLS.

A microRNA signature to predict risk progression of vulvar lichen sclerosus to squamous cell carcinoma

Borghi, Alessandro
Co-primo
;
D'Abundo, Lucilla
Co-primo
;
Bassi, Cristian;Lupini, Laura;Tagliatti, Valentina;Zedde, Pierantonia;Lanza, Giovanni;Gafà, Roberta;Negrini, Massimo;Corazza, Monica
2023

Abstract

Background: biomarkers useful for the identification of patients at risk of developing vulvar squamous cell carcinoma (VSCC) on a vulvar lichen sclerosus (VLS) background could lead to relevant prognostic advantages. To date, such biomarkers are not available. Objectives: we aimed to search for such biomarkers by evaluating the expression of microRNAs (miRNAs) in VLS samples that evolved or did not evolve into VSCCs. Methods: in this observational study, ten VLS samples that had not evolved into VSCC (VLS free from cancer, VLSfc) and 13 VLS samples that either had evolved into or were concomitant to high-risk HPV-negative VSCC (VLS cancer-associated, VLSca) were included. Total RNA, including miRNA, was isolated from formalin-fixed paraffin-embedded VLS samples. MiRNAseq analysis was employed to measure miRNA abundance. Differentially expressed miRNAs were identified using Qlucore Omics Explorer. To assess the risk prediction of each sample, the algorithm PAM (Prediction Analysis of Microarrays) was employed. The DIANA-mirPath database v.3 was used to identify biological pathways targeted by the differentially expressed microRNAs. Results: a smallRNA seq analysis conducted on 6 VLSca and 5 VLSfc samples revealed 163 differentially expressed miRNAs. By performing an independent smallRNA seq in a second set of samples (7 LVSca and 5 LVSfc) we assessed the capacity to discriminate between evolved and non-evolved VLS of a subpanel of 21 miRNAs. The results of PAM analysis showed that this set of 21 miRNAs correctly classified 19 out of the 23 samples (83%), with a probability close to 100% in most of the cases. The DIANA-mirPath database revealed the most significant pathways targeted by up- or down-regulated miRNAs, suggesting that a signature linked to cancer was already present in the VLSca samples. Conclusions: This study provided a strong indication that a selected subset of differentially expressed miRNAs exists between VLS that evolved and VLS that did not evolve towards cancer. MiRNA expression signature appears a potential early predictive biomarker of the risk of carcinogenesis in VLS.
2023
Borghi, Alessandro; D'Abundo, Lucilla; Bassi, Cristian; Lupini, Laura; Tagliatti, Valentina; Zedde, Pierantonia; Lanza, Giovanni; Gafà, Roberta; Negri...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2515530
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