Novel blood-based, five-gene biomarker set for the detection of colorectal cancer

Clin Cancer Res. 2008 Jan 15;14(2):455-60. doi: 10.1158/1078-0432.CCR-07-1801. Epub 2008 Jan 18.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Logistic Models
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Sensitivity and Specificity

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BANK1 protein, human
  • Biomarkers, Tumor
  • Membrane Proteins
  • NIBAN3 protein, human
  • Neoplasm Proteins
  • Cytidine Deaminase