Abstract
Collecting duct carcinoma (CDC) is a rare renal cell carcinoma subtype with a very poor prognosis. There have been only a few studies on gene expression analysis in CDCs. We compared the gene expression profiles of two CDC cases with those of eight normal tissues of renal cell carcinoma patients. At a threshold of |log2fold-change| ≥1, 3349 genes were upregulated and 1947 genes were downregulated in CDCs compared to the normal samples. Pathway analysis of the deregulated genes revealed that cancer pathways and cell cycle pathways were most prominent in CDCs. The most upregulated gene was keratin 17, and the most downregulated gene was cubilin. Among the most downregulated genes were four solute carrier genes (SLC3A1, SLC9A3, SLC26A7, and SLC47A1). The strongest negative correlations between miRNAs and mRNAs were found between the downregulated miR-374b-5p and its upregulated target genes HIST1H3B, HK2, and SLC7A11 and between upregulated miR-26b-5p and its downregulated target genes PPARGC1A, ALDH6A1, and MARC2. An upregulation of HK2 and a downregulation of PPARGC1A, ALDH6A1, and MARC2 were observed at the protein level. Survival analysis of the cancer genome atlas (TCGA) dataset showed for the first time that low gene expression of MARC2, cubilin, and SLC47A1 and high gene expression of KRT17 are associated with poor overall survival in clear cell renal cell carcinoma patients. Altogether, we identified dysregulated protein-coding genes, potential miRNA-target interactions, and prognostic markers that could be associated with CDC.
Highlights
Collecting duct renal cell carcinoma (CDC; known as Bellini duct carcinoma, collecting duct carcinoma of the kidney) is a very rare and very aggressive renal cell carcinoma with a median survival time of 11 months [1,2,3]
Based on the finding of a predominance of gene expression changes in solute carriers in Collecting duct carcinoma (CDC), and our previous results concerning miRNAs and their target gene expression as biomarkers in urologic cancers, we focused our analysis on these two research fields
It became evident that the two CDC samples formed a cluster that was very distinct from the normal tissue samples (Figure 2)
Summary
Collecting duct renal cell carcinoma (CDC; known as Bellini duct carcinoma, collecting duct carcinoma of the kidney) is a very rare (approximately 1–2%) and very aggressive renal cell carcinoma with a median survival time of 11 months [1,2,3]. There have been only a few reports about chromosomal aberrations, mutations in CDCs, and RNA expression changes [6,7,8]. In addition to the finding that the CDC transcriptome is unique and clustered with that of clear cell renal cell carcinoma (ccRCC) patients rather than UTUC patients, the authors compared CDCs with UTUCs and identified CDH6 and POU3F3 as the top upregulated genes and GATA3, TP63, KRT17, KRT7, KRT20, UPK2, UPK1A, and UPK3A as the top downregulated genes in CDCs [6]. RNA expression changes in members of the solute carrier (SLC) family, such as overexpression of SLC7A11 (cystine transporter, xCT), have been reported [8]
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