World J Mens Health.  2019 Sep;37(3):313-321. 10.5534/wjmh.180050.

No Causal Link between Phosphodiesterase Type 5 Inhibition and Melanoma

• Wang JZ
• Le S
• Alexanian
• Boddu S
• Merleev A
• Marusina A
• Maverakis

• KMID: 2455408
• DOI: http://doi.org/10.5534/wjmh.180050

Abstract

PURPOSE
To examine the association between phosphodiesterase type 5 (PDE5) inhibitor use and melanoma by 1) conducting a systematic review of observational studies; and 2) determining if low PDE5A gene expression in human melanoma correlated with decreased overall survival.
MATERIALS AND METHODS
A systematic search of observational studies examining the association between PDE5 inhibitor use and melanoma was performed through ClinicalTrials.gov, the Cochrane Library, EMBASE, PubMed, and Web of Science databases, and seven eligible studies were identified. PDE5A gene expression was analyzed with RNA sequencing data from 471 human melanoma samples obtained from The Cancer Genome Atlas.
RESULTS
Four studies reported a positive association between PDE5 inhibitor use and melanoma, and three studies found no correlation. RNA sequencing data analysis revealed that under-expression of the PDE5A gene did not impact clinical outcomes in melanoma.
CONCLUSIONS
There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.

Keyword

Melanoma; Phosphodiesterase 5 inhibitors; Sildenafil citrate; Tadalafil; Vardenafil dihydrochloride

MeSH Terms

Gene Expression
Genome
Guanosine Monophosphate
Humans
Melanoma*
Phosphodiesterase 5 Inhibitors
Sequence Analysis, RNA
Sildenafil Citrate
Statistics as Topic
Tadalafil
Vardenafil Dihydrochloride
Guanosine Monophosphate
Phosphodiesterase 5 Inhibitors
Sildenafil Citrate
Tadalafil
Vardenafil Dihydrochloride

Figure

• 

  Fig. 1 Kaplan-Meier survival curve for differential expression levels of PDE5A gene in (A) 470 patients (180 females and 290 males) with a diagnosis of melanoma at any tumor stage (0–IV), ages 14–91 years; and (B) specifically male melanoma patients (n=287) with a diagnosis of melanoma at any tumor stage (0–IV), ages 18–91 years. Melanoma prognosis unaffected by high or low PDE5A expression in patients, regardless of gender, age, or tumor stage.

• 

  Fig. 2 Flowchart of our database search and identification of eligible studies.

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