Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification

Abstract

To better understand the molecular mechanisms that underlie the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC), we studied the gene expression profiles of 29 ccRCC tumors obtained from patients with diverse clinical outcomes by using 21,632 cDNA microarrays. We identified gene expression alterations that were both common to most of the ccRCC studied and unique to clinical subsets. There was a significant distinction in gene expression profile between patients with a relatively nonaggressive form of the disease [100% survival after 5 years with the majority (15͞17 or 88%) having no clinical evidence of metastasis] versus patients with a relatively aggressive form of the disease (average survival time 25.4 months with a 0% 5-year survival rate). Approximately 40 genes most accurately make this distinction, some of which have previously been implicated in tumorigenesis and metastasis. To test the robustness and potential clinical usefulness of this molecular distinction, we simulated its use as a prognostic tool in the clinical setting. In 96% of the ccRCC cases tested, the prediction was compatible with the clinical outcome, exceeding the accuracy of prediction by staging. These results suggest that two molecularly distinct forms of ccRCC exist and that the integration of expression profile data with clinical parameters could serve to enhance the diagnosis and prognosis of ccRCC. Moreover, the identified genes provide insight into the molecular mechanisms of aggressive ccRCC and suggest intervention strategies.

CD10 is expressed in a subset of chromophobe renal cell carcinomas

“…Data about the expression profiling of renal epithelial neoplasms have been growing in the recent literature 15,[19][20][21][22] and the search for immunohistochemical markers uniquely positive for the most common renal cell neoplasms is extensive. 5,13,15,[22][23][24][25] CD10 has been suggested as a marker useful in the differential diagnosis of renal tumors.…”

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

“…It has also been suggested that expression of ET B is associated with improved outcome in patients with ccRCC. 16 Because it has been suggested that manipulation of the endothelin axis has potential in the treatment of various malignancies, including RCC, it is appropriate to understand the expression profile of the relevant genes in the various forms these tumors take. Previous studies of other genes have shown that expression profiles can differ significantly according to histologic subtype.…”

“…These include the hypervascular nature of ccRCC compared with the characteristically hypovascular appearance of PRCC, the presence of infiltrating lymphocytes and macrophages in PRCC but not in ccRCC, and the increased incidence of necrosis in patients with PRCC but not in patients with ccRCC. Distinct karyotypic aberrations also set these subtypes apart, such as loss of 3p in ccRCC compared with trisomies of 7,12,16,17, and 20 and loss of the Y chromosome in PRCC. 2,5,6 The endothelin axis comprises three endothelin peptides (ET-1, ET-2, and ET-3) and two cell-surface receptors (ET A and ET B ).…”

Genomics of renal cell cancer — Does it provide breakthrough?

“…49 The poor prognosis signature of RCC contained α2-macroglobulin, IGFBP7, TGFβRII, TIMP3 and phosphatidic acid phosphatase, while the good prognosis signature was defined by the expression of the oncogene FYN, oncosuppressor gene FAT, CDC42, autocrine motility factor, autotaxin (PDE1), the angiogenic cytokine PDGF-β and vessel markers CD31 and CD34. This study also defined an immunodiagnostic set of proteins (vimentin, CD74, parvalbumin and galectin-3) which can be used to differentiate between the classical RCC, its chromophobic variant and the oncocytoma.…”