Identification of collapsin response mediator protein-2 as a potential marker of colorectal carcinoma by comparative analysis of cancer cell secretomes

• Published in: Proteomics (Weinheim) Vol. 8; no. 2; pp. 316 - 332
• Main Authors: Wu, Chih-Ching, Chen, Hua-Chien, Chen, Su-Jen, Liu, Hao-Ping, Hsieh, Yi-Yueh, Yu, Chia-Jung, Tang, Reiping, Hsieh, Ling-Ling, Yu, Jau-Song, Chang, Yu-Sun
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.01.2008; WILEY-VCH Verlag; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Biomarkers, Tumor - analysis; Cell Line, Tumor; Colorectal carcinoma; Colorectal Neoplasms - secretion; CRMP-2; Electrophoresis, Polyacrylamide Gel; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Intercellular Signaling Peptides and Proteins - analysis; Male; Medical sciences; Middle Aged; Miscellaneous; Nerve Tissue Proteins - analysis; Proteins; Proteome - analysis; Secretome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor marker; Tumors; Rectal disease; Colorectal carcinoma; Colorectal cancer; Identification; Secretome; Malignant tumor; CRMP-2; Protein; Colonic disease; Tumor marker; Proteomics; Digestive diseases; Intestinal disease; Cancer
• ISSN: 1615-9853; 1615-9861
• DOI: 10.1002/pmic.200700819

The cancer cell secretome may contain many potentially useful biomarkers. We therefore sought to identify proteins in the conditioned media of colorectal carcinoma (CRC) cell lines but not in those from other cancer cell lines. The secretomes of 21 cancer cell lines derived from 12 cancer types were analyzed by SDS-PAGE combined with MALDI-TOF MS. Among the 325 proteins identified, collapsin response mediator protein-2 (CRMP-2) was chosen for evaluation as a potential CRC biomarker, since it was selectively detected in the CRC cell line secretome and has never been reported as a cancer biomarker. Immunohistochemical analysis of 169 CRC specimens showed that CRMP-2 was positively detected in 58.6% of the tumors, but weakly or not detected in >90% of the adjacent nontumor epithelial cells. Moreover, the CRMP-2-positive rate was significantly increased in earlier stage tumors and lymph node metastasis. Plasma CRMP-2 levels were significantly higher in CRC patients (N = 201) versus healthy controls (N = 201) (61.3 ± 34.6 vs. 40.2 ± 24.3 ng/mL, p = 0.001). Our results indicate that comparative analysis of cancer cell secretome is a feasible strategy for identifying potential cancer biomarkers, and that CRMP-2 may be a novel CRC biomarker.