Characterization of Leading Dysregulated Plasma-Proteome Associated Genes in Patients with Gastro-Esophageal Cancers
Frederick Vizeacoumar, Lynn Dwernychuk, Adnan Zaidi, Andrew Freywald, Franco Vizeacoumar, Shahid Ahmed
Background: Gastro-esophageal cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of gastro-esophageal cancers to identify new therapeutic targets and to yield predictive response to the available therapies. Our study aims to identify leading genes that are dysregulated (upregulated or downregulated) in patients with gastro-esophageal cancers.Methods: We examined gene expression data for those genes whose protein
... ts can be detected in the plasma in 600 independent tumor samples and 46 matching normal tissue samples using the Cancer Genome Atlas (TCGA) to identify leading genes that are dysregulated in patients with gastro-esophageal cancers. Non-parametric Mann-Whitney-U test was used to evaluate differential expression of genes using a cut-off of P< 0.05.Results: The comparison between tumors sample and healthy tissue showed BIRC5 (p=2.61 E-08), APOC2 (p=3.23E-08), CENPF (p=4.38E-08), STMN1 (p=5.74E-08), and HNRPC (p=8.21E-08) were the leading genes significantly overexpressed in esophageal cancer whereas CST1 (p=3.97 E-21), INHBA (p=9.22E-20), ACAN (p=1.08E-19), HSP90AB1 (p=2.62E-19), and HSPD1 (p=3.91E-19) were the leading genes that were overexpressed in stomach cancer. Conversely, C16orf89 (9.78E-08), AR (1.01E-07), CKB (1.17E-07), ADH1B (1.79E-07), and NCAM1 (2.15E-07) were the leading gene that were significantly downregulated in esophageal cancer whereas GPX3 (1.65E-19), CLEC3B (5.70E-19), CFD (5.68E-18), GSN (4.5IE-17), and CCL14 (1.12E-16) were significantly downregulated in stomach cancer. Furthermore, Stage-based examination showed stage-specific differential expression of various genes as well as stage-wise increasing or decreasing up-regulation or down-regulation of selected genes, respectively. Conclusions: The present study identified leading upregulated and downregulated genes in gastro-esophageal cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted-treatment.