Abstract
Сarcinoembryonic antigen (CEA, CEACAM5, CD66) is a promoter of metastasis in epithelial cancers that is widely used as a prognostic clinical marker of metastasis. The aim of this study is to identify the network of genes that are associated with CEA-induced colorectal cancer liver metastasis. We compared the genome-wide transcriptomic profiles of CEA positive (MIP101 clone 8) and CEA negative (MIP 101) colorectal cancer cell lines with different metastatic potential in vivo. The CEA-producing cells displayed quantitative changes in the level of expression for 100 genes (over-expressed or down-regulated). They were confirmed by quantitative RT-PCR. The KEGG pathway analysis identified 4 significantly enriched pathways: cytokine-cytokine receptor interaction, MAPK signaling pathway, TGF-beta signaling pathway and pyrimidine metabolism. Our results suggest that CEA production by colorectal cancer cells triggers colorectal cancer progression by inducing the epithelial- mesenchymal transition, increasing tumor cell invasiveness into the surrounding tissues and suppressing stress and apoptotic signaling. The novel gene expression distinctions establish the relationships between the existing cancer markers and implicate new potential biomarkers for colorectal cancer hepatic metastasis.
Highlights
Intestinal cancers rank fourth in cancer incidence in the world
In order to identify putative biological processes affected by changes in gene expression, we performed Gene Ontology enrichment analysis using the Gene Set Enrichment Analysis (GSEA) tool. 49 biological processes were functionally doi:10.1371/journal.pone.0161256.g001
Molecular pathways regulated by CEA over-expression were identified by pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG)
Summary
Intestinal cancers rank fourth in cancer incidence in the world. Despite the improvement of early diagnostics, 20% of primary colorectal cancer diagnoses reveal remote metastases. Available therapies still offer a poor prognosis and patients have a less than 10% five year survival rate [1]. The serum CEA test is recommended by the American Society of Clinical Oncology [2] and by the European Group on Tumor Markers [3] as a prognostic and postoperative. Transcriptome Analysis of Carcinoembryonic Antigen Producing Cancer Cells marker for metastases and as an aid in the management of cancer patients. Clinical efficacy of CEA screening has been demonstrated in the follow-up management of patients with colorectal, breast, lung, prostate, pancreatic and ovarian carcinoma [4]
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