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

作者：Mark Han, Choong Tsek Liew, Hong Wei Zhang, Samuel T. Chao, Run Zheng, Kok Thye Yip, Zhenya Song, Hiu Ming Li, Xiao Geng, Li Zhu, Jianjiang Lin, K. Wayne Marshall, Choong Chin Liew · 发表于：Clinical Cancer Research · 年份：2008 · DOI：10.1158/1078-0432.ccr-07-1801 · 被引用次数：124 · 研究领域：Genetic factors in colorectal cancer、Molecular Biology Techniques and Applications、Gene expression and cancer classification

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 ...