Identification of Four Serum miRNAs as Potential Markers to Screen for Thirteen Cancer Types

Abstract

Introduction: Cancer has consistently remained one of the top causes of death in the United States every year, with many cancer deaths preventable if detected early. Circulating serum miRNAs pose as a promising, minimally invasive supplement, or even alternative, to many current screening procedures. Many studies have shown that different serum miRNAs can discriminate healthy individuals from those with certain types of cancer. Although many of those miRNAs are often reported to be significant in one cancer type, they are also altered in other types of cancers. Currently, very few studies have investigated serum miRNA biomarkers for multiple different cancer types simultaneously for general cancer screening.Method: To identify serum miRNAs that would be useful in simultaneously screening multiple types of cancers, microarray cancer datasets were curated, yielding 13 different types of cancer with a total of 3352 cancer samples and 2809 non-cancer samples. The samples were then divided into discovery and validation sets. A hundred random forest models were built using the discovery set to select candidate miRNAs. The selected miRNAs were then used in the validation set to see how well they can differentiate cancer from normal samples in an independent dataset. Further analysis of the interactions between these miRNAs and their target mRNAs were investigated as well.Result: The random forest models achieved an average of 97% accuracy in the discovery set with 95% bootstrap confidence interval from 0.9544 to 0.9778. The selected miRNAs were hsa-miR-663a, hsa-miR-6802-5p, hsa-miR-6784-5p, hsa-miR-3184-5p, and hsa-miR-8073. Each individual miRNA exhibited high area under the curve (AUC) value using receiver operating characteristic analysis. Moreover, the combination of four out of the five miRNAs achieved the highest AUC value of 0.9815 with perfect sensitivity, indicating that these miRNAs have a high potential for cancer screening. miRNA-mRNA interaction and protein-protein interaction analysis provided insights into how these miRNAs may play a role in cancer in general.