Molecular characterization of circulating tumor cells in human metastatic colorectal cancer

• Published in: PloS one Vol. 7; no. 7; p. e40476
• Main Authors: Barbazán, Jorge, Alonso-Alconada, Lorena, Muinelo-Romay, Laura, Vieito, María, Abalo, Alicia, Alonso-Nocelo, Marta, Candamio, Sonia, Gallardo, Elena, Fernández, Beatriz, Abdulkader, Ihab, de Los Ángeles Casares, María, Gómez-Tato, Antonio, López-López, Rafael, Abal, Miguel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.07.2012; Public Library of Science (PLoS)
• Subjects: Analysis; Bioinformatics; Biology; Biomarkers; Biomarkers, Tumor - analysis; Cancer; Cancer metastasis; Cell adhesion & migration; Cell death; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - pathology; Detachment; Diagnostic systems; DNA microarrays; Gene expression; Genes; Genetic aspects; Humans; Hybridization; Laboratories; Leukemia; Liver; Liver Neoplasms - secondary; Lung carcinoma; Lung Neoplasms - secondary; Mechanical properties; Medical prognosis; Medicine; Metastases; Metastasis; Neoplastic Cells, Circulating - metabolism; Oligonucleotide Array Sequence Analysis; Oncology; Patients; Prognosis; Signaling; Stem cells; Transcriptome; Tumor cells; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040476

Metastatic colorectal cancer (mCRC) relies on the detachment of aggressive malignant cells from the primary tumor into the bloodstream and, concordantly, the presence of these Circulating Tumor Cells (CTC) is associated with a poor prognosis. In this work, the molecular characterization of CTC from mCRC patients was approached, with the aim of understanding their biology and improving their clinical utility in the management of colorectal cancer patients. For this, EpCAM-based immunoisolation of CTC was combined with whole transcriptome amplification and hybridization onto cDNA microarrays. Gene expression data from mCRC patients, once the background of unspecific immunoisolation from a group of controls had been subtracted, resulted in 410 genes that characterized the CTC population. Bioinformatics were used for the biological interpretation of the data, revealing that CTC are characterized by genes related to cell movement and adhesion, cell death and proliferation, and cell signalling and interaction. RTqPCR on an independent series of mCRC patients and controls was used for the validation of a number of genes related to the main cellular functions characterizing the CTC population. Comparison between primary carcinomas and lung and liver metastases further involved the CTC-genes in the promotion of metastasis. Moreover, the correlation of CTC-gene expression with clinical parameters demonstrated detection and prognosis significance. In conclusion, the molecular characterization of CTC from mCRC patients and the identification of diagnostic and prognostic biomarkers represent an innovative and promising approach in the clinical management of this type of patients.