title: Integrated Loss of miR-1/miR-101/miR-204 Discriminates Metastatic from Nonmetastatic Penile Carcinomas and Can Predict Patient Outcome.
abstract: OBJECTIVE
  Penile squamous cell carcinoma is a rare but aggressive cancer. Little is known about pivotal events in tumor pathogenesis and metastasis. Lymph node metastasis is the prevailing prognostic factor while clinical detection in patients remains difficult. Our aim was to identify distinct miRNAs that are differentially expressed in metastatic vs nonmetastatic penile carcinoma, which may serve as diagnostic biomarkers for disease progression.
  
  
  METHODS
  TaqMan® arrays and quantitative polymerase chain reaction were applied to analyze miRNA profiles in penile squamous cell carcinoma specimens and glans tissue from 24 patients. The prognostic value of deregulated miRNAs was analyzed using the Kaplan-Meier method. The Spearman test was applied to determine a potential linkage between distinctive miRNAs in individual patients.
  
  
  RESULTS
  Loss of miR-1 (p = 0.0048), miR-101 (p = 0.0001) and miR-204 (p = 0.0004) in metastasizing tumors and associated metastases (p = 0.0151, 0.0019 and 0.0003, respectively) distinguished patients with metastatic and nonmetastatic penile squamous cell carcinoma. These 3 miRNAs showed a coherent expression pattern. Consistently, patients with low levels of all 3 miRNAs had worse survival (p = 0.03). We identified a coordinately regulated miRNA target hub that is over expressed in penile squamous cell carcinoma and associated with lymphovascular invasion.
  
  
  CONCLUSIONS
  Our results provide evidence of a novel multiple miRNA based signature associated with lymph node metastasis and unfavorable prognosis of penile squamous cell carcinoma. The integrated loss of miR-1, miR-101 and miR-204 may predict the formation of metastases in penile cancer at an early stage.
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Juliane M
authors.initials: JM
authors.lastname: Hartz
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany. Electronic address: david.engelmann@med.uni-rostock.de.
authors.forename: David
authors.initials: D
authors.lastname: Engelmann
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fürst
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Marquardt
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Spitschak
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Goody
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Protzel
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Hakenberg
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research (JMH, DE, KF, SM, AS, DG, BMP), Rostock, Germany; Department of Urology, Rostock University Medical Center, Rostock, Germany.
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Pützer
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010412:Penile Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C544547:MIRN1 microRNA, human; C534072:MIRN101 microRNA, human; C549404:MIRN204 microRNA, human; D035683:MicroRNAs
keywords: carcinoma, squamous cell; microRNAs; mortality; neoplasm metastasis; penile neoplasms