Chengjian Tu1,2, Wilfrido Mojica3, Robert M Straubinger1,2, Jun Li1,2, Shichen Shen1,2, Miao Qu1,4, Lei Nie5, Rick Roberts6, Bo An1,2, Jun Qu1,2. 1. Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 2. New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA. 3. Department of Pathology, State University of New York at Buffalo-State, University of New York, Buffalo, NY, USA. 4. Beijing University of Chinese Medicine, Beijing, China. 5. School of Pharmaceutical Sciences, Shandong University, Jinan, China. 6. Department of Structural Biology, State University of New York at Buffalo, , State University of New York, Buffalo, NY, USA.
Abstract
PURPOSE: The heterogeneous structure in tumor tissues from colorectal cancer (CRC) patients excludes an informative comparison between tumors and adjacent normal tissues. Here, we develop and apply a strategy to compare paired cancerous (CEC) versus normal (NEC) epithelial cells enriched from patients and discover potential biomarkers and therapeutic targets for CRC. EXPERIMENTAL DESIGN: CEC and NEC cells are respectively isolated from five different tumor and normal locations in the resected colon tissue from each patient (N = 12 patients) using an optimized epithelial cell adhesion molecule (EpCAM)-based enrichment approach. An ion current-based quantitative method is employed to perform comparative proteomic analysis for each patient. RESULTS: A total of 458 altered proteins that are common among >75% of patients are observed and selected for further investigation. Besides known findings such as deregulation of mitochondrial function, tricarboxylic acid cycle, and RNA post-transcriptional modification, functional analysis further revealed RAN signaling pathway, small nucleolar ribonucleoproteins (snoRNPs), and infection by RNA viruses are altered in CEC cells. A selection of the altered proteins of interest is validated by immunohistochemistry analyses. CONCLUSION AND CLINICAL RELEVANCE: The informative comparison between matched CEC and NEC enhances our understanding of molecular mechanisms of CRC development and provides biomarker candidates and new pathways for therapeutic intervention.
PURPOSE: The heterogeneous structure in tumor tissues from colorectal cancer (CRC) patients excludes an informative comparison between tumors and adjacent normal tissues. Here, we develop and apply a strategy to compare paired cancerous (CEC) versus normal (NEC) epithelial cells enriched from patients and discover potential biomarkers and therapeutic targets for CRC. EXPERIMENTAL DESIGN:CEC and NEC cells are respectively isolated from five different tumor and normal locations in the resected colon tissue from each patient (N = 12 patients) using an optimized epithelial cell adhesion molecule (EpCAM)-based enrichment approach. An ion current-based quantitative method is employed to perform comparative proteomic analysis for each patient. RESULTS: A total of 458 altered proteins that are common among >75% of patients are observed and selected for further investigation. Besides known findings such as deregulation of mitochondrial function, tricarboxylic acid cycle, and RNA post-transcriptional modification, functional analysis further revealed RAN signaling pathway, small nucleolar ribonucleoproteins (snoRNPs), and infection by RNA viruses are altered in CEC cells. A selection of the altered proteins of interest is validated by immunohistochemistry analyses. CONCLUSION AND CLINICAL RELEVANCE: The informative comparison between matched CEC and NEC enhances our understanding of molecular mechanisms of CRC development and provides biomarker candidates and new pathways for therapeutic intervention.
Authors: Dalibor Antolovic; Luis Galindo; Anina Carstens; Nuh Rahbari; Markus W Büchler; Jürgen Weitz; Moritz Koch Journal: BMC Biotechnol Date: 2010-04-28 Impact factor: 2.563
Authors: A Rudolph; C Toth; M Hoffmeister; W Roth; E Herpel; L Jansen; A Marx; H Brenner; J Chang-Claude Journal: Br J Cancer Date: 2012-07-24 Impact factor: 7.640