Individualized analysis of differentially expressed miRNAs with application to the identification of miRNAs deregulated commonly in lung cancer tissues.

Identifying differentially expressed microRNAs (DE miRNAs) between cancer samples and normal controls is a common way to investigate carcinogenesis mechanisms. However, for a DE miRNA detected at the population-level, we do not know whether it is DE in a particular cancer sample. Here, based on the finding that the within-sample relative expression orderings of miRNA pairs are highly stable in a particular type of normal tissues but widely disrupted in the corresponding cancer tissues, we proposed a method, called RankMiRNA, to identify DE miRNAs in each cancer tissue compared with its own normal state. Evaluated with pair-matched miRNA expression profiles of cancer tissues and adjacent normal tissues for lung and liver cancers, RankMiRNA exhibited excellent performance. Finally, we exemplified an application of the individual-level differential expression analysis by finding miRNAs DE in at least 90% lung cancer tissues, defined as common DE miRNAs of lung cancer. After identifying DE miRNAs for each of 991 lung cancer samples from The Cancer Genome Atlas with RankMiRNA, we found that hsa-mir-210 was upregulated, while hsa-mir-490 and hsa-mir-486 were downregulated in > 90% of the 991 lung cancer samples. These common DE miRNAs were validated in independent pair-matched samples of cancer tissues and adjacent normal tissues measured with different platforms. In conclusion, RankMiRNA provides us a novel tool to find common and subtype-specific miRNAs for a type of cancer, allowing us to study cancer mechanisms in a novel way.