Clinical Validation of Colorectal Cancer Biomarkers Identified from Bioinformatics Analysis of Public Expression Data

• Published in: Clinical cancer research 2011-02, Vol.17 (4), p.700-709
• Main Authors: JUNG, Yeonjoo, LEE, Sanghyuk, CHUN, Ho-Kyung, WOO YONG LEE, KIM, Jaesang, CHOI, Hyung-Seok, KIM, Soon-Nam, LEE, Eunyoung, SHIN, Youngah, SEO, Jihae, KIM, Bumjin, JUNG, Yeonhwa, WAN KYU KIM
• Format: Article
• Language: English
• Subjects: Adenovirus E1A Proteins - genetics; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Bioinformatics; Biological and medical sciences; biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; c-Myc protein; Cell Line, Tumor; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Computational Biology; Computer programs; Data processing; Databases, Genetic; DEAD-box RNA Helicases - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Profiling - statistics & numerical data; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Humans; K-Ras protein; Male; Medical sciences; Middle Aged; Oncogenes; Pharmacology. Drug treatments; Polymerase chain reaction; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-myc - metabolism; Proto-Oncogene Proteins p21(ras) - metabolism; Ribosomal Proteins - genetics; RNA-mediated interference; Signal transduction; Statistical analysis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Therapeutic applications; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-10-1300

Identification of novel biomarkers of cancer is important for improved diagnosis, prognosis, and therapeutic intervention. This study aimed to identify marker genes of colorectal cancer (CRC) by combining bioinformatics analysis of gene expression data and validation experiments using patient samples and to examine the potential connection between validated markers and the established oncogenes such as c-Myc and K-ras. Publicly available data from GenBank and Oncomine were meta-analyzed leading to 34 candidate marker genes of CRC. Multiple case-matched normal and tumor tissues were examined by RT-PCR for differential expression, and 9 genes were validated as CRC biomarkers. Statistical analyses for correlation with major clinical parameters were carried out, and RNA interference was used to examine connection with major oncogenes. We show with high confidence that 9 (ECT2, ETV4, DDX21, RAN, S100A11, RPS4X, HSPD1, CKS2, and C9orf140) of the 34 candidate genes are expressed at significantly elevated levels in CRC tissues compared to normal tissues. Furthermore, high-level expression of RPS4X was associated with nonmucinous cancer cell type and that of ECT2 with lack of lymphatic invasion while upregulation of CKS2 was correlated with early tumor stage and lack of family history of CRC. We also demonstrate that RPS4X and DDX21 are regulatory targets of c-Myc and ETV4 is downstream to K-ras signaling. We have identified multiple novel biomarkers of CRC. Further analyses of their function and connection to signaling pathways may reveal potential value of these biomarkers in diagnosis, prognosis, and treatment of CRC.