Abstract
Background: Optimal molecular markers for detecting colorectal cancer (CRC) in a blood-based assay were evaluated. Microarray technology has shown a great potential in the colorectal cancer research. Genes significantly associated with cancer in microarray studies, were selected as candidate genes in the study. Pooling Internet public microarray data sets can overcome the limitation by the small number of samples in previous studies. Objective: Using public microarray data sets verifies gene expression profiles for colorectal cancer. Methods: Logistic regression analysis was performed, and odds ratios for each gene were determined between CRC and controls. Public microarray datasets of GSE 4107, 4183, 8671, 9348, 10961, 13067, 13294, 13471, 14333, 15960, 17538, and 18105 included 519 cases of adenocarcinoma and 88 controls of normal mucosa, which were used to verify the candidate genes from logistic models and estimated its external generality. Results: A 7-gene model of CPEB4, EIF2S3, MGC20553, MAS4A1, ANXA3, TNFAIP6 and IL2RB was pairwise selected that showed the best results in logistic regression analysis (H-L p=1.000, R2=0.951, AUC=0.999, accuracy=0.968, specificity=0.966 and sensitivity=0.994). Conclusions: A novel gene expression profile was associated with CRC and can potentially be applied to bloodbased detection assays.
Highlights
Optimal molecular markers for detecting colorectal cancer (CRC) in a blood-based assay were evaluated
A 7-gene model of CPEB4, EIF2S3, MGC20553, MAS4A1, ANXA3, TNFAIP6 and IL2RB was pairwise selected that showed the best results in logistic regression analysis (H-L p=1.000, R2=0.951, areas under the ROC curves (AUC)=0.999, accuracy=0.968, specificity=0.966 and sensitivity=0.994)
The logistic regression analysis further resulted in the selection of five genes of significance (i.e., P-value
Summary
Optimal molecular markers for detecting colorectal cancer (CRC) in a blood-based assay were evaluated. Conventional CRC screening tests include fecal occult blood testing, flexible sigmoidoscopy, doublecontrast barium enema X-ray, and colonoscopy [3]. They are commonly used, these tests have limitations, including highly variable sensitivity (i.e., 37% to 80%) and diet-test interactions [4]. The low sensitivities and specificities for these well-known genes are not considered acceptable for the detection of colorectal cancer. Multiple biomarkers were reported for the detection of colorectal cancer that delivered a better sensitivity or specificity [7,8]
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