Identification and Validation of Fibroblast Growth Factor 12 Gene as a Novel Potential Biomarker in Esophageal Cancer Using Cancer Genomic Datasets

Abstract

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.

Keywords: FGF12; MAPK8IP2; The Cancer Genome Atlas; esophageal cancer; in silico analysis.