Do Protocadherins Show Prognostic Value in the Carcinogenesis of Human Malignant Neoplasms? Systematic Review and Meta-Analysis
Thaís Torres Barros Dutra, Thâmara Manoela Marinho Bezerra, Ealber Carvalho Macedo Luna, Francisco Samuel Rodrigues Carvalho, Filipe Nobre Chaves, Paulo Barros Silva, Fábio Wildson Gurgel Costa, Karuza Maria Alves Pereira
Abstract
BACKGROUND: Protocadherins (PCDHs) have been reported as tumor suppressor genes, implying that these genes may be involved in tumor suppression in a variety of cancers. However, a thorough understanding of the functions and mechanisms of PCDHs remains limited. Our aim was to investigate the methylation profile of PCDHs in human malignant neoplasms. METHODS: This systematic review has been recorded in PROSPERO (#42019117844) and conducted according to PRISMA's checklist; search was conducted in LILACS, PubMed, Science Direct, Scopus, and Web of Science databases, manually, with search queries and without date or language restrictions. RESULTS: We found 91 articles, of which 26 were used for this meta-analysis and categorized according to the origin of the neoplasia. In total, 3,377 cases were compiled, with PCDH10, PCDH17, and PCDH8 being the most studied; males were 2.22 times more affected than females. Studies have shown significant heterogeneity (p <0.001), with the odds ratio varying between cases and controls [2.20 (95% CI = 1.11- 4.35) to 209.05 (95% CI = 12.64- 2,457.18)], and the value of association between methylation and cancers studied was 26.08 (95% CI = 15.42-44.13). CONCLUSION: In this systematic review, we have demonstrated using meta-analysis that PCDHs could emerge as potential tumor suppressor genes and that a significant increase in methylation may be useful for early detection of different cancers. This work may help in the identification of new prognostic biomarkers in malignant neoplasms.