Artikel
Identification of novel biomarkers for patients with renal cell carcinoma
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Autoren
Veröffentlicht: | 13. März 2015 |
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Gliederung
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Introduction: Renal cell carcinoma is one of the most common human malignancies. Despite of many efforts in the past, there is still no marker for diagnostic or prognostic purposes.
Methods: Microarray experiments were performed to determine the expression of 34,144 mRNA transcripts in 15 corresponding normal and malignant renal tissues. mRNA expression was validated using quantitative real-time PCR in 55 ccRCC and 52 normal renal specimen. siRNA mediated gene silencing was performed to study the functional relevance of dysregulated genes.
Results: We identified 1064 dysregulated transcripts (expression change >log2-fold; upregulated: 368, downregulated 696) in ccRCC tissue. Expression profiling allowed precise identification of ccRCC tissue based on a molecular signature. Dysregulation of 14 genes – so far not investigated in ccRCC – was confirmed using quantitative real-time PCR: upregulation of SLC6A3 (fold-change expression: mean 231-fold), NPTX2 (188-fold), TNFAIP6 (100-fold), NDUFA4L2 (78-fold), ENPP3 (42-fold), FABP6 (39-fold) and SPINK13 (26-fold), as well as downregulation of FXYD4 (2264-fold), SLC12A1 (863-fold), KNG1 (728-fold), NPHS2 (408-fold), SLC13A3 (68-fold), GCGR (27-fold), PLG (21-fold) in ccRCC tissue compared to normal renal tissue was observed. None of the investigated mRNAs was correlated with AJCC stage, pT-stage, metastasis nor grading (all p>0.03). mRNA levels were not correlated with RCC recurrence nor survival. siRNA-mediated knockdown of SLC6A3 and NDUFA4L2 did not influence cell proliferation.
Conclusion: We identified many novel mRNA transcripts dysregulated in ccRCC which may be useful as diagnostic biomarkers.