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Abstract Biomarkers predictive of drug-specific outcomes are important tools for personalized medicine. In this study, we present an integrative analysis to identify miRNAs that are predictive of drug-specific survival outcome in cancer. Using the clinical data from TCGA, we defined subsets of cancer patients who suffered from the same cancer and received the same drug treatment, which we call cancer-drug groups. We then used the miRNA expression data in TCGA to evaluate each miRNA’s ability to predict the survival outcome of patients in each cancer-drug group. As a result, the identified miRNAs are predictive of survival outcomes in a cancer-specific and drug-specific manner. Notably, most of the drug-specific miRNA survival markers and their target genes showed consistency in terms of correlations in their expression and their correlations with survival. Some of the identified miRNAs were supported by published literature in contexts of various cancers. We explored several additional breast cancer datasets that provided miRNA expression and survival data, and showed that our drug-specific miRNA survival markers for breast cancer were able to effectively stratify the prognosis of patients in those additional datasets. Together, this analysis revealed drug-specific miRNA markers for cancer survival, which can be promising tools toward personalized medicine. 

Novel discoveries of biomarkers predictive of drug-specific responses not only play a pivotal role in revealing the drug mechanisms in cancers, but are also critical to personalized medicine. In this study, we identified drug-specific biomarkers by integrating protein expression data, drug treatment data and survival outcome of 7076 patients from The Cancer Genome Atlas (TCGA). We first defined cancer-drug groups, where each cancer-drug group contains patients with the same cancer and treated with the same drug. For each protein, we stratified the patients in each cancer-drug group by high or low expression of the protein, and applied log-rank test to examine whether the stratified patients show significant survival difference. We examined 336 proteins in 98 cancer-drug groups and identified 65 protein-cancer-drug combinations involving 55 unique proteins, where the protein expression levels are predictive of drug-specific survival outcomes. Some of the identified proteins were supported by published literature. Using the gene expression data from TCGA, we found the mRNA expression of ∼11% of the drug-specific proteins also showed significant correlation with drug-specific survival, and most of these drug-specific proteins and their corresponding genes are strongly correlated.