Circulating microRNA expression in connection with prostate cancer lymphogenous metastasis

Abstract

Background. Lymph node metastases in prostate cancer (PC) are a negative prognostic factor. Non-invasive methods for their diagnostics are of primary importance. Objectives are identification of miRNA markers of lymph node metastases in plasma of PC patients and investigation of changes in primary tumors transcriptomes and plasma miRNA profiles during metastasis. Materials and methods. Plasma of 20 PC patients (10 with pN0M0 and 10 with pN1M0 stage) were collected and plasma miRNA expression was profiled on GeneChip miRNA 4.0 arrays (Affymetrix, USA). Target genes were searched for miRNAs with significant expression difference between pN0M0 and pN1M0 groups (fold change ≥2; p <0,05). In addition, bioinformatic analysis of 392 PC primary tumors transcriptomes from PRAD collection (ТCGA Research Network: http://cancergenome.nih.gov/) was done (318 for pN0M0 stage and 74 for pN1M0 stage). Results. The level of 17 miRNAs were significantly lower in plasma of pN1M0 group. Analysis of primary tumors expression profiles revealed 88 genes with significantly different expression between pN0M0 and pN1M0 groups (fold change ≥1,5; p <0,05). 11 of these genes are the potential targets of 17 miRNAs with lower levels in plasma of pN1M0 group. Interestingly, in most cases (8 out of 11) expression of these genes in primary tumor is elevated. Conclusion. The level of 17 miRNAs were significantly lower in plasma of PC patients with lymph nodes metastases (pN1M0). Analysis of primary tumor transcriptomes revealed a possible connection between miRNAs and their target genes levels in primary tumor and plasma. 17 plasma miRNAs found in this work could be a novel non-invasive markers of lymph nodes metastases in PC.