Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one.
The search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703.
Out of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR.
DNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies.
In this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.
European urology focus. 2024 Jun 19 [Epub ahead of print]
Mariana Silva-Ferreira, João A Carvalho, Sofia Salta, Teresa S Henriques, Pedro Pereira Rodrigues, Sara Monteiro-Reis, Rui Henrique, Carmen Jerónimo
Cancer Biology & Epigenetics Group, IPO Porto Research Center of IPO Porto (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center - Raquel Seruca (Porto.CCC) & CI-IPOP@RISE (Health Research Network), Porto, Portugal; Master Program in Oncology, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal., Cancer Biology & Epigenetics Group, IPO Porto Research Center of IPO Porto (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center - Raquel Seruca (Porto.CCC) & CI-IPOP@RISE (Health Research Network), Porto, Portugal; Doctoral Program in Medical Science, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal; Department of Urology & Urology Clinics, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal., Cancer Biology & Epigenetics Group, IPO Porto Research Center of IPO Porto (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center - Raquel Seruca (Porto.CCC) & CI-IPOP@RISE (Health Research Network), Porto, Portugal; Doctoral Program in Pathology and Molecular Genetics, ICBAS - School of Medicine and Biomedical Sciences - University of Porto, Porto, Portugal., CINTESIS@RISE - Health Research Network & MEDCIDS, Faculty of Medicine of the University of Porto, Porto, Portugal., Cancer Biology & Epigenetics Group, IPO Porto Research Center of IPO Porto (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center - Raquel Seruca (Porto.CCC) & CI-IPOP@RISE (Health Research Network), Porto, Portugal; Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), Porto, Portugal., Cancer Biology & Epigenetics Group, IPO Porto Research Center of IPO Porto (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center - Raquel Seruca (Porto.CCC) & CI-IPOP@RISE (Health Research Network), Porto, Portugal; Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Department of Pathology and Molecular Immunology, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal. Electronic address: ., Cancer Biology & Epigenetics Group, IPO Porto Research Center of IPO Porto (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center - Raquel Seruca (Porto.CCC) & CI-IPOP@RISE (Health Research Network), Porto, Portugal; Department of Pathology and Molecular Immunology, ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal. Electronic address: .