Five-gene Panel Research Articles

3611 Background: Human colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, and early detection is critical to improve prognosis. To date, we have applied our unique methodology (the Sentinel Principle) to identify blood-based gene expressed biomarkers for several diseases including osteoarthritis, bladder cancer and psychiatric disorders. In the present CRC study, we identified gene signatures from blood cells and characterized a set of biomarkers able to differentiate patients with CRC from controls. Methods: Microarray: 31 blood RNA sample (15 controls; 16 CRC) were profiled using Affymetrix U133Plus2.0 GeneChips. Differentially expressed genes were identified using the non-parametric, Wilcoxon-Mann-Whitney test. SYBR Green real-time RT-PCR: a subset of identified genes was assayed using 115 samples (57 controls; 58 CRC). Logistic regression was used to assess the ability of linear combinations of specific transcripts to distinguish CRC from controls. The diagnostic power for each combination was evaluated by AUC of the Receiver Operating Characteristic (ROC) curve. Blind Test: 83 samples were assayed (45 controls and 38 CRC). Results: Microarray data: 2,779 probes were significantly different in blood gene expression profiles from controls and those from CRC (p<0.05). Real-time RT-PCR: Two up-regulated genes (cytidine deaminase, 1.3 fold with p<0.001; MGC20553 /FERM domain containing 3, 1.2 fold with p=0.031) and three down-regulated genes were validated (B-cell scaffold protein with ankyrin repeats 1, 0.43 fold with p<0.001; B-cell novel protein 1, 0.44 fold with p<0.001; membrane-spanning 4-domains, subfamily A, member 1, 0.44 with p<0.001). Combination analysis: The AUC was 0.883 (95%, C.I. 0.810–0.935) for the best linear combination of these 5 genes. At a cut-off of -1.1, the sensitivity and specificity were 98% and 51%, respectively. Blind Test: The 5-gene set gave sensitivity of 95% (36/38) and specificity of 42% (19/45) with an overall accuracy of 66%. Conclusions: Gene expression signatures from peripheral blood differentiate between CRC patients and controls. The five-gene panel showed high classification performance and could be used as a novel screening tool for CRC. [Table: see text]

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