Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Abstract

Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3months and was compared to 20 LTS patients with a median OS of 55months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Here we characterized microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analyzed by next generation sequencing.The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS.Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal AUC above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time PCR in a validation cohort consisting of 20 STS and LTS patients.In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients.

Prognostic value of circulating microRNAs in upper tract urinary carcinoma

“…In accordance with our results, down-regulation of circulating miR-151b is described in primary CNS lymphoma patients [ 32 ]. Furthermore, in silico analysis shows that one of the target genes of miR-151b, CCNE1, is involved in T-cell signaling, cell-cycle, DNA-damage induced signaling and breast, pancreas, lung and prostate cancer pathways.…”

Role of miRNA‑21 in the diagnosis and prediction of treatment efficacy of primary central nervous system lymphoma

“…There is growing evidence to suggest that an imbalance in miRNA expression is evident in various types of cancer, and that miRNAs may act as oncogenes and tumor suppressor genes (5,14). Alterations in miRNA expression levels are apparent in various malignant tumors, including leukemia and lymphoma, thus miRNAs are increasingly used as diagnostic and prognostic markers (15)(16)(17). The direct extraction of miRNAs from tumor samples (18) and simple detection of circulating miRNAs in human serum or plasma is also advantageous.…”

miRCarta: a central repository for collecting miRNA candidates

“…This class of short non-coding RNAs with an average length of 17–23 nucleotides can bind to their complementary target mRNAs and repress their translation or mediate their degradation ( 1 – 3 ). Since one miRNA potentially regulates many genes and may therefore severely influence the overall regulation network, their expression changes have been the focus of many publications describing various diseases ( 4 – 8 ) and are discussed as potential biomarkers ( 9 – 13 ).…”