Abstract
Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC.
Highlights
Prostate cancer (PC) is a leading cause of cancer mortality in men and the most commonly diagnosed male malignancy [1]
The gene network was selected by an integrative approach combining mRNA expression profiles, copy number alteration (CNA), and miRNA expression levels. miRNAs controlling this network could be potential biomarkers for PC theranostic applications
To better clarify the genes and miRNAs which are altered in aggressive PC versus normal samples (NS) and the role of these genes and miRNAs in PC development, we initially found the mRNAs altered in aggressive PC versus NS (I approach) with CNA (II approach), reducing the number of interesting genes from 3069 to 38 (Table 1)
Summary
Prostate cancer (PC) is a leading cause of cancer mortality in men and the most commonly diagnosed male malignancy [1]. Previous studies reported that expression of oncogenes might be increased as a result of DNA amplification, and expression of tumor suppressor genes might be inactivated by physical deletions of DNA sequences [26,27,28,29,30,31] Epigenetic alterations, such as miRNA level changes, are frequent in PC [4]. The combination of gene expression, CNAs, and miRNA expression was approached in few studies and only in some cancer diseases, but not in PC, leading to interesting results in terms of tumour classification [38,39,40,41,42,43,44]. The gene network was selected by an integrative approach combining mRNA expression profiles, CNAs, and miRNA expression levels. miRNAs controlling this network could be potential biomarkers for PC theranostic applications
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