The Genome-Wide Analysis of Carcinoembryonic Antigen Signaling by Colorectal Cancer Cells Using RNA Sequencing

Olga Bajenova; Anna Gorbunova; Igor Evsyukov; Michael Rayko; Svetlana Gapon; Ekaterina Bozhokina; Alexander Shishkin; Stephen J O'Brien

doi:10.1371/journal.pone.0161256

The Genome-Wide Analysis of Carcinoembryonic Antigen Signaling by Colorectal Cancer Cells Using RNA Sequencing

PLoS One. 2016 Sep 1;11(9):e0161256. doi: 10.1371/journal.pone.0161256. eCollection 2016.

Authors

Olga Bajenova^{1

2}, Anna Gorbunova¹, Igor Evsyukov¹, Michael Rayko¹, Svetlana Gapon³, Ekaterina Bozhokina⁴, Alexander Shishkin⁵, Stephen J O'Brien^{1

6}

Affiliations

¹ Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia.
² Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg, Russia.
³ Boston Children's Hospital, Boston, MA, United States of America.
⁴ Institute of Cytology RAS, St. Petersburg, Russia.
⁵ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.
⁶ Oceanographic Center, 8000 N. Ocean Drive, Nova Southeastern University, Ft Lauderdale, Florida, 33004, United States of America.

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.

Publication types

Validation Study

MeSH terms

Carcinoembryonic Antigen / metabolism*
Cell Line, Tumor
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / immunology
Gene Expression Profiling
Genome-Wide Association Study*
Humans
Polymerase Chain Reaction
Sequence Analysis, RNA / methods*

Substances

Carcinoembryonic Antigen

Grants and funding

This work was financially supported by the Russian Foundation for Fundamental Research, grant RFFI # 11-04-01711 to OB, by the Government of the Russian Federation mega grant 11G34.31.0068 to SO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.