11363
2014
eng
article
1
2015-05-21
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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
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.
10.1371/journal.pone.0109877
urn:nbn:de:bvb:20-opus-113633
PLoS ONE 9(10): e109877. doi:10.1371/journal.pone.0109877
Daniel Claudius Vergho
Susanne Kneitz
Charis Kalogirou
Maximilian Burger
Markus Krebs
Andreas Rosenwald
Martin Spahn
Andreas Löser
Arkadius Kocot
Hubertus Riedmiller
Burkhard Kneitz
eng
uncontrolled
forecasting
eng
uncontrolled
metastasis
eng
uncontrolled
renal cancer
eng
uncontrolled
renal cell carcinoma
eng
uncontrolled
kidneys
eng
uncontrolled
surgical oncology
eng
uncontrolled
surgical and invasive medical procedures
eng
uncontrolled
regression analysis
Medizin und Gesundheit
open_access
Urologische Klinik und Poliklinik
Pathologisches Institut
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11363/146_Vergho_PLoS.pdf
11006
2014
eng
article
1
2015-02-25
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Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma
Background
Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs.
Methods
Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC).
Results
RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease.
Conclusions
A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.
10.1186/1471-2407-14-25
urn:nbn:de:bvb:20-opus-110061
In: BMC Cancer 14:25 (2014). doi:10.1186/1471-2407-14-25
Daniel Vergho
Susanne Kneitz
Andreas Rosenwald
Charlotte Scherer
Martin Spahn
Maximilian Burger
Hubertus Riedmiller
Burkhard Kneitz
eng
uncontrolled
Renal cell carcinoma
eng
uncontrolled
RCC
eng
uncontrolled
Kidney cancer
eng
uncontrolled
miRNA
eng
uncontrolled
miR-21
eng
uncontrolled
miR-126
eng
uncontrolled
Prognosis
eng
uncontrolled
Profiling
eng
uncontrolled
Biomarker
eng
uncontrolled
Tumour markers
Medizin und Gesundheit
open_access
Urologische Klinik und Poliklinik
Pathologisches Institut
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11006/005_Vergho_BMCCancer.pdf