Identification and Validation of Fibroblast Growth Factor 12 Gene as a Novel Potential Biomarker in Esophageal Cancer Using Cancer Genomic Datasets
Identification and Validation of Fibroblast Growth Factor 12 Gene as a Novel Potential Biomarker in Esophageal Cancer Using Cancer Genomic Datasets
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DOI：
10.1089/omi.2017.0116
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发表时间：
2017-10-01
影响因子：
3.3
通讯作者：
Saxena, Sunita
中科院分区：
文献类型：
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作者：
Bhushan, Ashish;Singh, Avninder;Saxena, Sunita
食管鳞状细胞癌（ESCC）具有复杂的多因素病因，其中环境、地理和遗传因素起主要作用。它是印度男性中第二常见的癌症，女性中第四常见的癌症，在印度东北部的患病率特别高。在这项研究中，使用了一种综合的计算机模拟方法[大卫、NCG 5.0、Oncomine、Cancer Cell Line Encyclopedia和The Cancer Genome Atlas（TCGA）]，通过使用印度东北部ESCC的三个可用基因组数据集，然后对其进行体外功能验证，来鉴定潜在的生物标志物。成纤维细胞生长因子12（FGF12）基因在食管鳞癌中呈高表达。在TCGA OncoPrint门户网站的ESCC上也观察到FGF12的上调，而在GTEx数据库上的正常食管组织中定位了FGF12基因的极低表达。FGF12的沉默表现出对肿瘤细胞增殖、集落形成和细胞迁移活性的显著抑制。FGF12的上调显示ESCC患者的存活率显著降低。蛋白质相互作用分析发现FGF12与MAPK8IP2和MAPK13结合。FGF 12沿着MAPK 8IP 2和MAPK 13蛋白的高表达与ESCC患者的不良生存相关。组织芯片也显示这些蛋白质在食管鳞癌患者中的表达。这些结果表明，FGF12在ESCC中具有潜在的作用，并表明应用计算机模拟方法的癌症基因组数据集有助于生物标志物发现研究，广泛而具体地，用于鉴定FGF12作为ESCC中的推定生物标志物。
Esophageal squamous cell carcinoma (ESCC) has a complex, multifactorial etiology in which environmental, geographical, and genetic factors play major roles. It is the second most common cancer among men and the fourth most common among women in India, with a particularly high prevalence in Northeast India. In this study, an integrative in silico [DAVID, NCG5.0, Oncomine, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas (TCGA)] approach was used to identify the potential biomarkers by using the available three genomic datasets on ESCC from Northeast India followed by its in vitro functional validation. Fibroblast Growth Factor 12 (FGF12) gene was overexpressed in ESCC. The upregulation of FGF12 was also observed on ESCC of TCGA OncoPrint portal, whereas very low expression of FGF12 gene was mapped in normal esophageal tissue on the GTEx database. Silencing of FGF12 showed significant inhibition in activity of tumor cell proliferation, colony formation, and cell migration. The upregulation of FGF12 showed significantly reduced survival in ESCC patients. The protein interaction analysis of FGF12 found the binding with MAPK8IP2 and MAPK13. High expression of FGF12 along with MAPK8IP2, and MAPK13 proteins correlate with poor survival in ESCC patients. Tissue microarray also showed expression of these proteins in patients with ESCC. These results indicate that FGF12 has a potential role in ESCC and suggest that cancer genomic datasets with application of in silico approaches are instrumental for biomarker discovery research broadly and specifically, for the identification of FGF12 as a putative biomarker in ESCC.