Molecular Research in Penile Cancer—Lessons Learned from the Past and Bright Horizons of the Future?

Protzel, Chris; Spiess, Philippe E.

doi:10.3390/ijms141019494

Cited by 16 publications

(12 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PeCa has an unpredictable outcome, and its current treatment requires partial or total penile amputation. There are few molecular studies on PeCa, with the majority of them having focused on protein expression levels or genetic/epigenetic alterations of specific genes [ 11 , 12 ]. DNA methylation, histone modification, and regulation by non-coding RNA regulate gene expression by controlling chromatin accessibility and transcription [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

BackgroundDespite 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).ResultsGenome-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.ConclusionsA 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0082-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Besides, a few genes during carcinogenesis, proliferation, invasion and metastasis of PeCa have been identified. For instance, p53, cyclin-dependent kinase inhibitor 2A (CDKN2A) and matrix metallopeptidase 9 (MMP-9) were proven to play crucial roles in PeCa carcinogenic routes and epithelial-mesenchymal transition (EMT), respectively [ 5 ]. Nonetheless, as mentioned above, additional comprehensive research to further elucidate the exact mechanisms of molecular changes underlying the initiation, development and progression of PeCa is imperative for us to explore novel and valuable preventive, early detection, targeted therapies and prognosis prediction approaches for this genitourinary disorder.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing

et al. 2015

View full text Add to dashboard Cite

Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis.

show abstract

“…In a study by Gunia et al, p21 and cyclin D1 were not significantly associated with disease‐specific mortality in multivariate analysis . The major pathways and mediators involved in the development of penile preneoplastic lesions and neoplasms are listed in Table …”

Section: Molecular and Pathophysiological Pathways In Penile Cancermentioning

confidence: 99%

“…In contrast, in HPV‐negative tumors, p53 is mutated and may be independently associated with lymph node metastases (Fig. ) …”

Section: Molecular and Pathophysiological Pathways In Penile Cancermentioning

confidence: 99%

See 1 more Smart Citation

Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies

Spiess

Dhillon

Baumgarten

et al. 2016

CA A Cancer J Clinicians

View full text Add to dashboard Cite

Answer questions and earn CME/CNE Squamous cell carcinoma (SCC) of the penis is a rare malignancy in the United States, with a significantly higher incidence-up to 20 to 30 times greater-in areas of Africa and South America. This can be explained in part by the significantly greater prevalence of sexually transmitted diseases among high-risk males often having unprotected sex with multiple sexual partners. Human papillomavirus (HPV) has been implicated as the infectious pathway by which several these penile neoplasms originate from precursor lesions. In this regard, a fundamental understanding of HPV in penile carcinogenesis can have meaningful implications in understanding 1) the diagnosis of HPV-related precursor penile lesions, 2) targeting HPV-specific molecular pathways, and 3) cancer prevention. Using vaccination programs not only may improve patient outcomes but also may minimize the need for highly aggressive and often debilitating surgical resection. CA Cancer J Clin 2016. © 2016 American Cancer Society.

show abstract

Molecular Research in Penile Cancer—Lessons Learned from the Past and Bright Horizons of the Future?

Cited by 16 publications

References 55 publications

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

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

MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing

Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies

Contact Info

Product

Resources

About