Molecular characterization of clear cell renal cell carcinoma identifies CSNK 2A1, SPP 1 and DEFB 1 as promising novel prognostic markers

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2016-05, Vol.124 (5), p.372-383
• Main Authors: Rabjerg, Maj, Bjerregaard, Henriette, Halekoh, Ulrich, Jensen, Boye L., Walter, Steen, Marcussen, Niels
• Format: Article
• Language: English
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/apm.12519

The prognosis associated with clear cell renal carcinoma (cc RCC ) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice. Here we hypothesized that we, using TaqMan ® Array, could identify superior prognostic messenger RNA (mRNA) s in long‐term follow‐up. Messenger RNA level of 19 candidate genes was investigated in 97 patients with cc RCC . Three genes impacted significantly on prognosis in both univariate and multivariate analysis. In univariate analysis, CSNK 2A1 was a strong indicator of a poor overall survival (OS) ( HR = 5.01, p < 0.001), disease specific survival (DSS) ( HR = 6.21, p = 0.007) and progression free survival ( PFS ) ( HR = 5.93, p = 0.005). High expression of SPP 1 was associated to poor PFS ( HR = 4.41, p = 0.04). DEFB 1 was associated with a better PFS ( HR = 0.24, p = 0.006). In multivariate analysis, CSNK 2A1 was associated to a worse OS ( HR = 3.56, p = 0.008) and PFS ( HR = 3.84, p = 0.005), whereas SPP 1 was an independent predictor of a worse PFS ( HR = 3.46, p = 0.007) and DEFB 1 of a better PFS ( HR = 0.37, p = 0.027). These results show that with TaqMan ® Array we could identify three superior gene products related to prognosis. Further studies are needed to elucidate the pathways and roles of these genes in renal cancer development.