Abstract
540 Background: Collecting duct carcinoma (CDC) of the kidney is a rare tumor, originating from renal medulla, characterized by younger age at diagnosis and poor prognosis. Since targeted therapies are currently not available for CDC, we aimed to identify the most deregulated pathways in this type of cancer to gain insights into new molecular targets. Methods: Total RNA was extracted from FFPE samples of primary CDC (n=9), clear cell carcinoma (CCC, n=7) and healthy normal (n=7) adjacent renal tissues (23 total samples). Gene expression profile was performed by GeneChip Human Transcriptome Array 2.0 (HTA 2.0 -Affymetrix). The One-Way between-subject ANOVA algorithm was used to calculate statistical significances of pairwise comparisons. Transcripts with a linear fold change (f.c.) of <-2/>2 (p-value<0.05) were included in the study. Functional enrichment analysis identified the most deregulated pathways in CDC. Results: A total of 1,079 genes (827 coding, 252 non-coding) were significantly deregulated comparing CDC, CCC and normal kidney (p<0.05). In CDC vs normal tissue comparison, 484 genes (339 coding, 145 non-coding) are significantly up-regulated, and 49 (40 coding, 9 non-coding) down regulated in tumors (p<0.05). The 4 most highly expressed transcripts in CDC are currently unknown, requiring further studies. Among the most altered known transcripts, we identified FN1 (f.c. 6.33), miR-21 (f.c. 4.01), KNG1 (f.c. -9.4) and AQP2 (f.c. -6.03), whose deregulation was previously associated with advanced disease and lower survival in renal cancer, supporting the quality of our analysis. Functional enrichment analysis indicated a strong downregulation of transcripts associated with histone modifications, function of cytoplasmic ribosomal proteins, senescence, autophagy and focal adhesion in CDC vs both CCC and normal tissues. Conclusions: Our analysis identifies several coding and non-coding transcripts differentially expressed in CDC vs CCC and normal kidney, resulting in alteration of a number of cellular pathways associated with cancer pathogenesis, progression and prognosis. These results pave the way to a deeper understanding of a rare tumor as CDC, driving the development of new, targeted therapies for this aggressive disease.
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