In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer.
In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer.
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DOI：
10.3390/ijms19030910
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发表时间：
2018-03-19
影响因子：
5.6
通讯作者：
Castiglioni I
中科院分区：
文献类型：
--
作者：
Cava C;Bertoli G;Colaprico A;Bontempi G;Mauri G;Castiglioni I
与其他癌症疾病一样，前列腺癌（PC）是由细胞中遗传变异的积累引起的，这些遗传变异驱动了恶性生长。这些改变通过基因分析和拷贝数改变（CNA）分析来揭示。此外，最近的证据表明microRNA在PC发育中也起着重要作用。尽管对PC进行了研究，但与疾病发展和进展相关的改变（基因，CNA和miRNA）和生物学过程仍然部分难以捉摸。许多被提出作为癌症诊断或预后工具的基因标签很少重叠。鉴定功能相关的共表达基因，可以以更好的重复性鉴定与PC相关的基因的核心网络。通过结合不同的方法，包括mRNA表达谱，CNA和miRNA表达水平的整合，我们确定了与其他已发表的基因签名重叠的四个基因的基因签名，并能够在计算机上区分高Gleason评分的PC和正常人体组织，通过基因共表达分析进一步富集到19个基因。通过对可能调控该网络的miRNAs的分析，我们发现hsa-miR-153与网络中的基因高度相关。我们的研究结果确定了一个四基因签名与诊断和预后价值的PC，并提出了一个有趣的基因网络，可以发挥关键的调控作用，PC的发展和进展。此外，控制该网络的hsa-miR-153可能是高Gleason评分PC中治疗诊断剂的潜在生物标志物。
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.
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影响因子：
5.6
作者：
Bertoli G;Cava C;Castiglioni I
通讯作者：
Castiglioni I
DOI：
10.1186/2043-9113-4-2
发表时间：
2014-01-24
期刊：
Journal of clinical bioinformatics
影响因子：
--
作者：
Cava C;Zoppis I;Gariboldi M;Castiglioni I;Mauri G;Antoniotti M
通讯作者：
Antoniotti M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8.4
作者：
Ciatto, S;Zappa, M;Gervasi, G
通讯作者：
Gervasi, G
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H