J Urol. 2016 Aug;196(2):570-8.

Integrated loss of miR-1/-101/-204 discriminates metastatic from non-metastatic penile carcinomas and can predict patient outcome.

Hartz JM, Engelmann D, Fürst K, Marquardt S, Spitschak A, Goody D, Protzel C, Hakenberg OW, Pützer BM.

Abstract


PURPOSE: Penile squamous cell carcinoma (PSCC) is a rare but aggressive cancer and little is known about pivotal events in tumor pathogenesis and metastasis. Occurrence of lymph node metastases is the prevailing prognostic factor while their clinical detection in patients remains difficult. Our aim was to identify distinct miRNAs differentially expressed in metastatic versus non-metastatic penile carcinomas that may serve as diagnostic biomarkers for disease progression. MATERIALS AND METHODS: TaqMan arrays and qPCR were applied to analyze miRNA profiles in PSCC specimens and glans tissue from 24 patients. Prognostic value of deregulated miRNAs was analysed using the Kaplan-Meier method. Spearman's test was applied to reveal a potential linkage between distinctive miRNAs in individual patients. RESULTS: We observed that loss of miR-1 (p = 0.0048), miR-101 (p = 0.0001) and miR-204 (p = 0.0004) in metastasising tumors and associated metastases (p = 0.0151, p = 0.0019, p = 0.0003) distinguished between patients with metastatic and non-metastatic PSCC. These three miRNAs exhibited a coherent expression pattern and consistently patients with low levels of all three miRNAs had worse survival (p = 0.03). We identified a coordinately regulated miRNA target hub overexpressed in PSCCs, which is associated with lymphovascular invasion. CONCLUSIONS: Our results provide evidence for a novel multiple miRNA-based signature associated with lymph node metastasis and unfavorable prognosis of PSCC. The integrated loss of miR-1, -101 and -204 may predict formation of metastases in penile cancer at an early stage.