Annals of Surgical Oncology

, Volume 21, Issue 3, pp 1046–1054 | Cite as

MicroRNAs with Prognostic Potential for Metastasis in Clear Cell Renal Cell Carcinoma: A Comparison of Primary Tumors and Distant Metastases

  • Joana Heinzelmann
  • André Unrein
  • Ulrike Wickmann
  • Sophie Baumgart
  • Marcus Stapf
  • Attila Szendroi
  • Marc-Oliver Grimm
  • Mieczyslaw R. Gajda
  • Heiko Wunderlich
  • Kerstin Junker
Urologic Oncology

Abstract

Background

MicroRNAs (miRNAs) are regulators of gene expression in tumor development and progression. However, their influence on metastasis of clear cell renal cell carcinoma (ccRCC) is less understood. To determine the role of miRNAs in metastatic progression, miRNA expression in primary ccRCC was compared to distant metastases.

Methods

Total RNA of 53 primary ccRCCs, 35 distant metastases from lung, bone, brain, and abdomen, as well as 17 normal kidney tissues was isolated from fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) samples. The miRNA microarrays were performed based on fresh frozen tissue. Results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on fresh frozen tissue and FFPE samples. Real-time cell analyses and transwell invasion assays were carried out after transient transfection of microRNA-30c (miR-30c) in cell line 786-O.

Results

There were 14 miRNAs differently expressed in metastatic primary ccRCC and distant metastases compared to non-metastatic primary tumors. A strong correlation of miRNAs to progression-free- and cancer-specific 5-year-survival was determined. Specific miRNAs were differently expressed in distant metastases compared to primary ccRCC. A miRNA signature distinguished lung metastases from other metastatic sites. Overexpression of miR-30c increased adherence and decreased migration and invasion in the ccRCC cell line.

Conclusions

MiRNAs are deregulated in metastatic primary ccRCC and could be promising prognostic markers for an early prediction of metastasis. Alterations in miRNA expression characterize distant metastases of different metastatic sites. Furthermore, our study suggests a functional role of miR-30c in metastasis. The miRNAs could be a helpful tool for individual follow-up prediction and personalized therapy selection.

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Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Joana Heinzelmann
    • 1
    • 2
  • André Unrein
    • 2
  • Ulrike Wickmann
    • 2
  • Sophie Baumgart
    • 1
    • 2
  • Marcus Stapf
    • 2
  • Attila Szendroi
    • 3
  • Marc-Oliver Grimm
    • 2
  • Mieczyslaw R. Gajda
    • 4
  • Heiko Wunderlich
    • 5
    • 2
  • Kerstin Junker
    • 1
    • 2
  1. 1.Clinic of Urology and Pediatric UrologySaarland University Medical CenterHomburg/SaarGermany
  2. 2.Department of UrologyJena University HospitalJenaGermany
  3. 3.Clinic of UrologySemmelweis University BudapestBudapestHungary
  4. 4.Institute of PathologyJena University HospitalJenaGermany
  5. 5.Clinic of Urology and Pediatric UrologyEisenach St. Georg HospitalEisenachGermany

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