An 18-gene blood-based IVD test for colorectal cancer early detection with high sensitivity and specificity.

Abstract

3551 Background: Colorectal cancer (CRC) is often curable particularly diagnosed at early stages. Different screening strategies are in place in various counties. However, the compliance rate with current CRC screening recommendations remains poor. A simple blood-based IVD test would represent an interesting alternative. We previously reported a 100-gene signature for early detection of CRC using microarray technology. Based on this result, we have developed a new blood test with real-time PCR technology. Methods: 144 CRC cases and 153 Controls were enrolled. A total of 52 genes were selected as candidate markers to be transferred from microarray to real-time PCR. The gene expression profiles from 100 CRC cases and 100 Controls were used as a training set for signature discovery. Signature identification process was conducted by Minimum Redundancy Maximum Relevance (mRMR) feature selection method and Support Vector Machine (SVM) classification algorithm under the Leave-One-Out Cross Validation (LOOCV) framework. The optimal size of signature was determined by a stepwise inclusion selection procedure which started with one gene and repeatedly added genes one by one until all genes were included. The performance of each N-gene signature by the LOOCV was estimated and used to determine the best size of signature. Results: The gene expression profiles measured by microarray and real-time PCR technology were highly comparable and resulted in a significant correlation in term of fold change ratio between CRC cases and Controls (Pearson’s Correlation Coefficient = 0.95). An 18-gene signature was identified and validated in an independent validation set with 44 CRC cases and 53 Controls. The performance of 18-gene signature in the validation set reached 88.7% accuracy (95%CI: 0.80-0.94), 88.6% sensitivity (95%CI: 0.75-0.96), and 88.7% specificity (95%CI: 0.76-0.95). Conclusions: Our new results demonstrated the feasibility of technology transfer from microarray to real-time PCR. The blood test could be offered to individuals who are unwilling or unable to undergo colonoscopy to increase the CRC screening compliance rate. Meanwhile, its high specificity could also help to avoid unnecessary colonoscopies.