Background: Many studies have demonstrated the promising utility of DNA methylation and miRNA as biomarkers for colorectal cancer (CRC) early detection. However, mRNA is rarely reported. This study aimed to identify novel fecal-based mRNA signatures.
Methods: The differentially expressed genes (DEGs) were first determined between CRCs and matched normal samples by integrating multiple datasets. Then, Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to reduce the number of candidates of aberrantly expressed genes. Next, the potential functions were investigated for the candidate signatures and their ability to detect CRC and pan-cancers was comprehensively evaluated.
Results: We identified 1841 common DEGs in two independent datasets. Functional enrichment analysis revealed they were mainly related to extracellular structure, biosynthesis, and cell adhesion. The CRC classifier was established based on six genes screened by LASSO regression. Sensitivity, specificity, and area under the ROC curve (AUC) for CRC detection were 79.30%, 80.40%, and 0.85 (0.76-0.92) in the training set, and these indexes achieved 93.20%, 41.80%, and 0.73 (0.65-0.83) in the testing set. For validation set, the sensitivity, specificity, and AUC were 98.90%, 98.00%, and 0.97 (0.94-0.99). The average sensitivities exceeded 90.00% for CRCs with different clinical features. For adenomas detection, the sensitivity and specificity were 74.50% and 64.00%. Besides, the six genes obtained an average AUC of 0.855 for pan-cancer detection.
Conclusion: The six-gene signatures showed ability to detect CRC and pan-cancer samples, which could be served as potential diagnostic markers.
Copyright © 2022 Peijie Wu et al.