Secreted and Cell Surface Genes Expressed in Benign and Malignant Colorectal Tumors

Phillip Buckhaults, Carlo Rago, Brad St. Croix, Katharine E. Romans, Saurabh Saha, Lin Zhang, Bert Vogelstein and Kenneth W. Kinzler

Howard Hughes Medical Institute [P. B., C. R., B. V.] and Johns Hopkins Oncology Center [B. S. C., K. E. R., S. S., L. Z., B. V., K. W. K.], Johns Hopkins Medical Institutions, Baltimore, Maryland 21231

Cancer Res 2001 Oct 1;61(19):6996-7001

Serial analysis of gene expression was used to identify transcripts encoding secreted or cell surface proteins that were expressed in benign and malignant tumors of the colorectum. A total of 290,394 tags were analyzed from normal, adenomatous, and cancerous colonic epithelium. Of the 21,343 different transcripts observed, 957 were found to be differentially expressed between normal tissue and adenoma or between normal tissue and cancer. Forty-nine transcripts were elevated 20-fold in adenomas, 40 transcripts were elevated 20-fold in cancers, and 9 transcripts were elevated 20-fold in both. Products of six of these nine transcripts (TGFBI, LYS, RDP, MIC-1, REGA, and DEHL) were predicted to be secreted or to reside on the cell surface, and these were analyzed in more detail. The abnormal expression levels predicted by serial analysis of gene expression were confirmed by quantitative PCR analyses of each of these six genes. Moreover, the cell types responsible for the elevated expression were identified by in situ hybridization and by PCR analyses of epithelial cells immunoaffinity purified from primary tumors. This study extends knowledge of the differences in gene expression that underlie various stages of neoplasia and suggests specific diagnostic approaches that may be useful for the early detection of colorectal neoplasia.