Do Protocadherins Show Prognostic Value in the Carcinogenesis of Human Malignant Neoplasms? Systematic Review and Meta-Analysis

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.