RNAs não codificantes no câncer de vulva: revisão sistemática de potenciais biomarcadores associados ao diagnóstico e prognóstico

Abstract

Vulvar cancer (VC) is a rare gynecological neoplasm characterized by etiological and molecular

heterogeneity, particularly between human papillomavirus (HPV)-associated and HPV- independent tumors. In this context, non-coding RNAs (ncRNAs) have been investigated

because of their involvement in gene regulation and tumor progression and their possible use as biomarkers. This study aimed to identify and synthesize the available evidence on ncRNAs associated with VC, considering their biological roles and diagnostic and prognostic potential. A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) recommendations and registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420261406196. Searches were performed in PubMed, Scopus, Web of Science, and Latin American and Caribbean Literature in Health Sciences (LILACS), considering studies published between 2010 and 2025. A total of 238 records were identified, of which 78 were removed as duplicates. After screening 160 records and assessing 19 full-text articles, eight studies were included in the qualitative synthesis. Five studies primarily investigated microRNAs (miRNAs), two examined long non-coding RNAs (lncRNAs), and one analyzed

circular RNAs (circRNAs). Among the main findings, reduced expression of miR-30c and let- 7a was related to increased HMGA2 expression and tumor invasiveness; miR-223-5p and miR- 19b-1-5p showed lower expression in tumors with lymph node metastasis; and increased miR- 182-5p expression promoted proliferation, migration, invasion, and epithelial-mesenchymal

transition. The lncRNAs MALAT1 and MEG3 and a set of circulating miRNAs showed potential to distinguish vulvar squamous cell carcinoma (VSCC) from non-tumor samples or precursor lesions. In addition, the UCA1/miR-103a/WEE1 axis was associated with cisplatin resistance, whereas circRNAs presented exploratory findings related to HPV-positive tumors. It is concluded that ncRNAs may contribute to the biological and clinical characterization of VC, although their application as biomarkers requires validation in larger and independent studies.