Downregulation of serum microRNA-205 as a potential diagnostic and prognostic biomarker for human glioma

Abstract

G lioma is the most common primary intracranial tumor in adults, accounting for more than 40% of primary CNS neoplasms. In accordance with WHO classification, which is based on histomorphological criteria, gliomas are categorized as well-differentiated low-grade astrocytoma (WHO Grade I or II), anaplastic astrocytoma (WHO Grade III), or glioblastoma (GBM; WHO Grade IV). 15 The most frequent and malignant glioabbreviatioNs GBM = glioblastoma; KPS = Karnofsky Performance Scale; miR-205 = microRNA 205; miRNA = microRNA; OS = overall survival; PCNSL = primary diffuse large B-cell lymphoma of the CNS; qRT-PCR = quantitative reverse-transcription polymerase chain reaction. obJective Circulating microRNAs (miRNAs) are a new class of highly promising cancer biomarkers. Malignant glioma is one of the most devastating and lethal forms of intrinsic CNS tumor. Here, the authors evaluated serum miRNA 205 (miR-205) levels in patients with glioma. methods Sixty-four patients in whom glioma was diagnosed and 45 healthy controls were recruited between October 2011 and March 2012 and randomly assigned to the screening cohort or the validation cohort. Cohorts of patients with other brain tumors, including meningioma (n = 8), primary diffuse large B-cell lymphoma of the CNS (n = 6), and pituitary adenoma (n = 5), were investigated and compared. miR-205 extraction from serum was detected by real-time quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was applied to perform survival analysis, the risk factors were analyzed by using a Cox regression model, and the receiver operating characteristic working curve was used to analyze the value of miR-205 in the prognostic evaluation of the patients. results The authors first demonstrated that serum miR-205 expression was significantly lower in patients with glioma than in healthy controls (p < 0.001). It is important to note that serum miR-205 expression demonstrated a stepwise decrease with ascending pathological grades. The serum miR-205 biomarker had high sensitivity, specificity, and accuracy in patients with glioma. Serum levels of miR-205 were identified as an individual diagnostic marker and were significantly lower in the glioma cohort than in the other brain tumor cohorts. Serum miR-205 levels were significantly increased in postoperative samples over those in the preoperative samples and were reduced again during glioblastoma recurrences. Statistical analysis revealed a significant correlation between low serum miR-205 expression and both ascending pathological grades (p = 0.002) and low Karnofsky Performance Scale scores (p = 0.01). Patients with glioma at an advanced pathological grade (Grade III or IV) and a higher miR-205 serum level showed longer overall survival than those with a lower miR-205 serum concentration (p < 0.01). Furthermore, Cox regression analysis revealed that miR-205 serum levels were independently associated with overall survival. coNclusioNs These data indicate that serum miR-205 expression is a novel and valuable bioma...

Serum microRNA profiling in patients with glioblastoma: a survival analysis

“…A number of studies have investigated the potential role of circulating miRNAs in glioma survival and clinical outcomes [24, 25, 27, 29, 30]. For example, Zhi et al reported that up regulation of serum miR-20a-5p, miR-106a-5p, and miR-181b-5p was associated with advanced clinical stages of astrocytoma, and high expression of serum miR-19a-3p, miR-106a-5p, and miR-181b-5p was significantly associated with poor patient survival among astrocytoma patients [29].…”

“…Profiling of miRNAs circulating in serum or plasma may be particularly useful in glioblastoma patients, given the risks of sequential surgery and biopsy, and the lack of readily usable biomarkers to predict clinical outcome. Previous attempts have been made to assess circulating miRNAs in relation to glioblastoma prognosis [24–30]. However, due to small sample size and a heterogeneous patient population, prognostic impact could not be elucidated.…”

The role of micro-RNA in the regulation of signal pathways in gliomas

“…Так, уровни циркулирующих miR-128, -205 и -451a были ниже в сыворотке крови больных глиомами по сравнению с контролем или пациентами с менингиомой [120][121][122]. Анализ с использованием микрочипов и qPCR, ROC-кривых показал, что одновременное определение уровня экспрессии miR-15b и miR-21 в сыворотке крови помогает дифференцировать пациентов с глиомами от больных с другими поражениями головного мозга (метастазами и др.)…”

MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics

“…In a study of 64 glioma patients, serum miR‐205 levels displayed a stepwise decrease with ascending tumor grade and additionally increased following surgery and decreased again during tumor recurrence. Further, patients with advanced pathological grade demonstrated longer overall survival times when serum miR‐205 levels were elevated 101, 102. Thus, serum miRNAs could serve as critical indicators of disease progression and outcome.…”