title: Impact of miR-21, miR-126 and miR-221 as prognostic factors of clear cell renal cell carcinoma with tumor thrombus of the inferior vena cava.
abstract: Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.
authors.affiliation: Department of Urology and Pediatric Urology, Julius Maximilians University Medical Center, Würzburg, Germany.
authors.forename: Daniel Claudius
authors.initials: DC
authors.lastname: Vergho
authors.affiliation: Physiological Chemistry I, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kneitz
authors.affiliation: Department of Urology and Pediatric Urology, Julius Maximilians University Medical Center, Würzburg, Germany.
authors.forename: Charis
authors.initials: C
authors.lastname: Kalogirou
authors.affiliation: Department of Urology, University of Regensburg, Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.affiliation: Department of Urology and Pediatric Urology, Julius Maximilians University Medical Center, Würzburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krebs
authors.affiliation: Department of Pathology, Comprehensive Cancer Center Mainfranken (CCCM), University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Department of Urology, University Hospital Bern, Bern, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Spahn
authors.affiliation: Department of Urology and Pediatric Urology, Julius Maximilians University Medical Center, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Löser
authors.affiliation: Department of Urology and Pediatric Urology, Julius Maximilians University Medical Center, Würzburg, Germany.
authors.forename: Arkadius
authors.initials: A
authors.lastname: Kocot
authors.affiliation: Department of Urology and Pediatric Urology, Julius Maximilians University Medical Center, Würzburg, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Riedmiller
authors.affiliation: Department of Urology and Pediatric Urology, Julius Maximilians University Medical Center, Würzburg, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kneitz
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology*; D014682:Vena Cava, Inferior / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; C527111:MIRN126 microRNA, human; C524940:MIRN21 microRNA, human; C525709:MIR221, human