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Novel Blood-Based, Five-Gene Biomarker Set for the Detection of Colorectal Cancer

Authors' Affiliations: ¹ GeneNews Corporation, Toronto, Canada; ² Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China; ³ Lam Wah Ee Hospital, Penang, Malaysia; ⁴ Department of Digestive Medicine, 2nd Affiliated Hospital of Medical College of Zhejiang University; ⁵ Department of Colorectal Surgery, 1st Affiliated Hospital of Medical College of Zhejiang University, Hangzhou, China; ⁶ Department of Surgery, 1st Affiliated Hospital, Anhui Medical University, Hefei, China; and ⁷ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Choong Chin Liew, GeneNews Corporation, 2 East Beaver Creek Road, Building 2, Richmond Hill, Ontario, Canada L4B 2N3. Phone: 617-834-4371; E-mail: cliew{at}genenews.com.

Purpose: We applied a unique method to identify genes expressed in whole blood that can serve as biomarkers to detect colorectal cancer (CRC).

Experimental Design: Total RNA was isolated from 211 blood samples (110 non-CRC, 101 CRC). Microarray and quantitative real-time PCR were used for biomarker screening and validation, respectively.

Results: From a set of 31 RNA samples (16 CRC, 15 controls), we selected 37 genes from analyzed microarray data that differed significantly between CRC samples and controls (P < 0.05). We tested these genes with a second set of 115 samples (58 CRC, 57 controls) using quantitative real-time PCR, validating 17 genes as differentially expressed. Five of these genes were selected for logistic regression analysis, of which two were the most up-regulated (CDA and MGC20553) and three were the most down-regulated (BANK1, BCNP1, and MS4A1) in CRC patients. Logit (P) of the five-gene panel had an area under the curve of 0.88 (95% confidence interval, 0.81-0.94). At a cutoff of logit (P) >+0.5 as disease (high risk), <–0.5 as control (low risk), and in between as an intermediate zone, the five-gene biomarker combination yielded a sensitivity of 94% (47 of 50) and a specificity of 77% (33 of 43). The intermediate zone contained 22 samples. We validated the predictive power of these five genes with a novel third set of 92 samples, correctly identifying 88% (30 of 34) of CRC samples and 64% (27 of 42) of non-CRC samples. The intermediate zone contained 16 samples.

Conclusion: Our results indicate that the five-gene biomarker panel can be used as a novel blood-based test for CRC.