A cross-cancer metastasis signature in the microRNA-mRNA axis of paired tissue samples

Abstract

In the progression of cancer, cells acquire genetic mutations that cause uncontrolled growth. Over time, the primary tumour may undergo additional mutations that allow for the cancerous cells to spread throughout the body as metastases. Since metastatic development typically results in markedly worse patient outcomes, research into the identity and function of metastasisassociated biomarkers could eventually translate into clinical diagnostics or novel therapeutics. Although the general processes underpinning metastatic progression are understood, no consistent nor clear cross-cancer biomarker profile has yet emerged. However, the literature suggests that some microRNAs (miRNAs) may play an important role in the metastatic progression of several cancer types. Using a subset of The Cancer Genome Atlas (TCGA) data, we performed an integrated analysis of mRNA and miRNA expression with paired metastatic and primary tumour samples to interrogate how the miRNA-mRNA regulatory axis influences metastatic progression. From this, we successfully built mRNAand miRNA-specific classifiers that can discriminate pairs of metastatic and primary samples across 11 cancer types. In addition, we identified a number of miRNAs whose metastasis-associated dysregulation could predict mRNA metastasis-associated dysregulation. Among the most predictive miRNAs, we found several previously implicated in cancer progression, including miR-301b, miR-1296, and miR-423. Taken together, our results suggest that cross-cancer metastatic samples have unique biomarker signatures when compared with paired primary tumours, and that these miRNA biomarkers can be used to predict both metastatic status and mRNA expression.