Author:
Santos Renan da Silva,Hirth Carlos Gustavo,Pinheiro Daniel Pascoalino,Bezerra Maria Júlia Barbosa,Silva-Fernandes Isabelle Joyce de Lima,Paula Dayrine Silveira de,Alves Ana Paula Negreiros Nunes,Moraes Filho Manoel Odorico de,Moura Arlindo de Alencar Araripe,Lima Marcos Venício Alves,Pessoa Claudia do Ó,Furtado Cristiana Libardi Miranda
Abstract
Abstract
Background
Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC).
Results
The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33–3.38).
Conclusions
P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.
Funder
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Genetics,Molecular Biology
Reference78 articles.
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49.
2. de Souza MAC, Zacchi SR, Viana KCG, de Souza CB, Zandonade E, Amorim MHC. Survival analysis of penile cancer patients treated at a tertiary oncology hospital. Cienc e Saude Coletiva. 2018;23:2479–86.
3. Eduardo C, Cardona M, García-perdomo HA. Incidence of penile cancer worldwide: systematic review and meta-analysis. Pan Am J Public Heal. 2017;2:1–10.
4. Bandini M, Ahmed M, Basile G, Watkin N, Master V, Zhu Y, et al. A global approach to improving penile cancer care. Nat Rev Urol. 2022;19:231–9.
5. Brito HO, de Calixto JRR, Medeiros R, da Costa RMG. Comment on DKK1 inhibits canonical Wnt signaling in human papillomavirus-positive penile cancer cells. Transl Oncol. 2022;16:2021–2.
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