摘要
食管鳞状细胞癌(ESCC),是食管癌最常见的亚型,也是全球第六大癌症死亡原因,五年来生存率为19%。高效生物标记物的识别有助于早期检测和更好的了解ESCC分子机制,从而降低死亡率。然而,适合临床诊断和预后的生物标志物还没有被定义。在本研究中,我们采用一个系统的、整体的“组学”策略来重构转录调控和蛋白质-蛋白质相互作用的网络,确定新的生物标志物,潜在的分子靶点和ESCC的转录调控机制。为此,我们发现作为食管癌特异性标志物的30个下调,21个上调表达的基因,因为在五个不同的数据集中,91例ESCC肿瘤样本与正常组织相比,这些基因表达有差异。我们首次报告了ACPP,c2orf54,dynlt3,ENDOU,FMO2和Kank1(下调基因)和COL10A1,fndc3b,Homer3、MARCKSL1、和RFC4(上调基因)与ESCC之间的联系。此外,ESCC驱动的分子通路也构建了疾病分子机制的阐明;特别是当信号通路上调时,许多代谢通路下调。此外,报导的ESCC代谢物被进行了分析,并通过花生四烯酸代谢和激素的生物合成途径确定了代谢功能障碍。多组学网络策略能发现新的生物标志物和ESCC患者个人靶向药物。
关键词: 系统生物学,生物医学,功能基因组学,食管鳞状细胞癌,生物标志物。
Current Cancer Drug Targets
Title:Proteomic and Metabolic Signatures of Esophageal Squamous Cell Carcinoma
Volume: 16 Issue: 8
Author(s): Kubra Karagoz, Heather L. Lehman, Douglas B. Stairs, Raghu Sinha, Kazim Y. Arga
Affiliation:
关键词: 系统生物学,生物医学,功能基因组学,食管鳞状细胞癌,生物标志物。
摘要: Esophageal squamous cell carcinoma (ESCC), which is the most common subtype of esophageal cancers, is the sixth leading cause of cancer deaths worldwide with a five-year survival rate of 19%. Identification of efficient biomarkers for early detection and better understanding of the molecular mechanisms of ESCC may offer reduced mortality. However, proper biomarkers for clinical diagnosis and prognosis have not been defined yet. In the presented study, we employed a systematic and integrative ‘omics’ strategy to reconstruct networks of transcriptional regulation and protein-protein interaction to identify novel biomarkers, potential molecular targets, and mechanisms of transcriptional control in ESCC. Towards this end, we revealed 30 down-regulated and 21 upregulated genes as ESCC specific biomarkers since these were differentially expressed between 91 ESCC tumor samples compared to normal tissues in five different datasets. We report the association of ACPP, C2orf54, DYNLT3, ENDOU, FMO2, and KANK1 (down-regulated genes) and COL10A1, FNDC3B, HOMER3, MARCKSL1, and RFC4 (up-regulated genes) to ESCC for the first time. Further, the ESCC driven molecular pathways were also constructed to elucidate the molecular mechanism of the disease; specifically several metabolic pathways were down-regulated while the signaling pathways were up-regulated. Additionally, reporter metabolites for ESCC were analyzed and metabolic dysfunction was ascertained in arachidonic acid metabolism and steroid hormone biosynthesis pathways. The multi-omics network strategy presented here may enable discovery of novel biomarkers and targets for personalized medicine in ESCC patients.
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Cite this article as:
Kubra Karagoz, Heather L. Lehman, Douglas B. Stairs, Raghu Sinha, Kazim Y. Arga , Proteomic and Metabolic Signatures of Esophageal Squamous Cell Carcinoma, Current Cancer Drug Targets 2016; 16 (8) . https://dx.doi.org/10.2174/1568009616666160203113721
DOI https://dx.doi.org/10.2174/1568009616666160203113721 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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