Genome-wide methylation and transcriptome analysis in penile carcinoma: uncovering new molecular markers

Clinical Epigenetics

Silvia Regina Rogatto⁵  Zdenko Herceg⁷  Gustavo Cardoso Guimarães⁴  Ademar Lopes⁴  Eliney Ferreira Faria⁶  Cristovam Scapulatempo-Neto¹  Fabio Albuquerque Marchi²  Mateus Camargo Barros-Filho⁸  Hector Hernandez-Vargas⁷  Ariane Fidelis Busso⁸  Ilce Mara de Syllos Cólus³  Hellen Kuasne³ 

[1] Department of Pathology, CPOM - Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil;Inter-institutional Grad Program on Bioinformatics, Institute of Mathematics and Statistics, USP, São Paulo, SP, Brazil;Department of Biology, Londrina State University, Londrina, PR, Brazil;Department of Pelvic Surgery, AC Camargo Cancer Center, São Paulo, Brazil;Department of Urology, Faculty of Medicine, UNESP, Botucatu, SP, Brazil;Department of Urology, Barretos Cancer Hospital, Barretos, SP, Brazil;Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France;CIPE - International Research Center, AC Camargo Cancer Center, Rua Taguá, 440, CEP: 01508-010, Liberdade, São Paulo, SP, Brazil

关键词: Transcriptome;    Molecular marker;    Human papillomavirus;    DNA methylome;    Penile carcinomas;   

Others  :  1210208
DOI  :  10.1186/s13148-015-0082-4

 received in 2014-10-30, accepted in 2015-04-06,  发布年份 2015

【 摘 要 】

Background

Despite penile carcinoma (PeCa) being a relatively rare neoplasm, it remains an important public health issue for poor and developing countries. Contrary to most tumors, limited data are available for markers that are capable of assisting in diagnosis, prognosis, and treatment of PeCa. We aimed to identify molecular markers for PeCa by evaluating their epigenomic and transcriptome profiles and comparing them with surrounding non-malignant tissue (SNT) and normal glans (NG).

Results

Genome-wide methylation analysis revealed 171 hypermethylated probes in PeCa. Transcriptome profiling presented 2,883 underexpressed and 1,378 overexpressed genes. Integrative analysis revealed a panel of 54 genes with an inverse correlation between methylation and gene expression levels. Distinct methylome and transcriptome patterns were found for human papillomavirus (HPV)-positive (38.6%) and negative tumors. Interestingly, grade 3 tumors showed a distinct methylation profile when compared to grade 1. In addition, univariate analysis revealed that low BDNF methylation was associated with lymph node metastasis and shorter disease-free survival. CpG hypermethylation and gene underexpression were confirmed for a panel of genes, including TWIST1, RSOP2, SOX3, SOX17, PROM1, OTX2, HOXA3, and MEIS1.

Conclusions

A unique methylome signature was found for PeCa compared to SNT, with aberrant DNA methylation appearing to modulate the expression of specific genes. This study describes new pathways with the potential to regulate penile carcinogenesis, including stem cell regulatory pathways and markers associated to a worse prognosis. These findings may be instrumental in the discovery and application of new genetic and epigenetic biomarkers in PeCa.

【 授权许可】

   
2015 Kuasne et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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