Biomarcadores de metilação de DNA no rastreio do cancro do colo do útero

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Biomarcadores de metilação de DNA no rastreio do cancro do colo do útero

Quarta, 15.12.2021

O rastreio do cancro do colo do útero continua a ser essencial para controlar a incidência e mortalidade associados a esta neoplasia. Atualmente, este rastreio é baseado na pesquisa e genotipagem de Vírus do Papiloma Humano (HPV) de alto risco. Este método é altamente sensível, mas a sua especificidade é limitada. Assim, neste estudo, os investigadores do IPO do Porto e da Administração Regional de Saúde do Norte avaliaram marcadores de metilação de DNA em amostras incluídas em parafinas e em citologias cervicais em meio líquido para triagem de mulheres positivas para HPV de alto risco. Esses marcadores foram capazes de identificar lesões HSIL+ com alta especificidade e boa sensibilidade. Assim, este teste molecular pode ser uma ferramenta importante para aumentar a relação custo-eficácia do Programa de rastreio do cancro do colo do útero do Norte de Portugal.

 

Autores e Afiliações:

Sofia Salta1,2, Leonardo Maia-Moço1, Helena Estevão-Pereira1, José Pedro Sequeira1,3, Renata Vieira1,4, Carla Bartosch1,4,5, Sara Petronilho1,4,5, Paula Monteiro4, Ana Sousa4,6, Inês Baldaque 7, Jéssica Rodrigues 8,9, Hugo Sousa 6,7, Fernando Tavares 10, Rui Henrique 1,4,5, Carmen Jerónimo1,5

1Cancer Biology & Epigenetics Group, IPO Porto Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

2Doctoral Program in Molecular Pathology and Genetics, School of Medicine and Biomedical Sciences -University of Porto (ICBAS-UP), 4050-313, Porto, Portugal.

3Master in Oncology, School of Medicine and Biomedical Sciences-University of Porto (ICBAS-UP), 4050-313, Porto, Portugal.

4Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

5Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513, Porto, Portugal

6Molecular Oncology and Viral Pathology Group, IPO Porto Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

7Virology Service, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

8Cancer Epidemiology Group, IPO Porto Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal

9Centre of Mathematics (CMAT), University of Minho, Campus de Gualtar, 4710 - 057 Braga, Portugal

10Administração Regional de Saúde do Norte, I.P., Rua de Santa Catarina 1288, 4000-477, Porto, Portugal.

 

Abstract:

Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation-based markers as triage test for women hr-HPV+ in the population-based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa-miR124-2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low-grade intraepithelial squamous lesions [LSIL], 59 high-grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr-HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MALme , FAM19A4me and hsa-miR124-2me methylation levels were disclosed in histological HSIL or worse (HSIL+) in testing set. Individually, markers depicted over 86% specificity for HSIL+ detection. In validation set, all these genes significantly differed between histological HSIL+ and low-grade squamous intraepithelial lesions or less. In combination, these markers reached 74% specificity and 61% sensitivity for identification of histological HSIL+. We concluded that host gene methylation might constitute a useful referral triage tool of hr-HPV+ women enrolled in the Cervical Cancer Screening Program of Northern Portugal.

 

Revista: International Journal of Cancer

 

Link: https://onlinelibrary.wiley.com/doi/10.1002/ijc.33778