MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i) to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma–associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.
MicroRNAs are key regulators of cancer and development. We can use their pattern of expression to classify different cancers or in our case different stages in cancer development. We used a novel method to define progressive stages for Kaposi sarcoma (KS), which is a cancer of the endothelial cells. We identified specific precursor-miRNAs that accurately identify stages of KS tumor progression. For the first time, we were able to profile KS patient material. This is difficult to come by, but it is more closely related to the human cancer than even the best cell culture models. Our work statistically defined clusters of pre-miRNAs, each signifying one step in cancer progression. This is the first time that precursor miRNAs profiling was used to define cancer stages. It is also the first time that we have defined makers of any kind that allow us to distinguish between different types of the endothelial cancer KS. Loss of mir-221 precursor miRNA and gain of mir-15 precursor miRNA expression demarked the transition from merely immortal to fully tumorigenic cells. Mir-140 and Kaposi sarcoma–associated herpesvirus viral microRNAs increased progressively with the degree of transformation, i.e. more aggressive stages expressed higher levels of these biomarkers. High levels of the precursor microRNA mir-24 emerged as a biomarker only in patient derived KS samples, not in any of the culture models.