Novel blood-based, five-gene biomarker set for the detection of colorectal cancer.
OBJECTIVE
We applied a unique method to identify genes expressed in whole blood that can serve as biomarkers to detect colorectal cancer (CRC).


METHODS
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.


CONCLUSIONS
Our results indicate that the five-gene biomarker panel can be used as a novel blood-based test for CRC.
Han
Mark
M
GeneNews Corporation, Toronto, ON, Canada.
Liew
Choong Tsek
CT
Zhang
Hong Wei
HW
Chao
Samuel
S
Zheng
Run
R
Yip
Kok Thye
KT
Song
Zhen-Ya
ZY
Li
Hiu Ming
HM
Geng
Xiao Ping
XP
Zhu
Li Xin
LX
Lin
Jian-Jiang
JJ
Marshall
K Wayne
KW
Liew
Choong Chin
CC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016015:Logistic Models; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C447641:BANK1 protein, human; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C477321:NIBAN3 protein, human; D009363:Neoplasm Proteins; D003564:Cytidine Deaminase