Unique Interplay between Molecular miR-181b/d Biomarkers and Health Related Quality of Life Score in the Predictive Glioma Models

Abstract

In the last decade, an increasing amount of research has been conducted analyzing microRNA expression changes in glioma tissue and its expressed exosomes, but there is still sparse information on microRNAs or other biomarkers and their association with patients’ functional/psychological outcomes. In this study, we performed a combinational analysis measuring miR-181b and miR-181d expression levels by quantitative polymerase chain reaction (qPCR), evaluating isocitrate dehydrogenase 1 (IDH1) single nucleotide polymorphism (SNP), and O-6-methylguanine methyltransferase (MGMT) promoter methylation status in 92 post-surgical glioma samples and 64 serum exosomes, including patients’ quality of life evaluation applying European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-30), EORTC the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), and the Karnofsky performance status (KPS). The tumoral expression of miR-181b was lower in grade III and glioblastoma, compared to grade II glioma patients (p < 0.05). Additionally, for the first time, we demonstrated the association between miR-181 expression levels and patients’ quality of life. A positive correlation was observed between tumoral miR-181d levels and glioma patients’ functional parameters (p < 0.05), whereas increased exosomal miR-181b levels indicated a worse functional outcome (p < 0.05). Moreover, elevated miR-181b exosomal expression can indicate a significantly shorter post-surgical survival time for glioblastoma multiforme (GBM) patients. In addition, both tumoral and exosomal miR-181 expression levels were related to patients’ functioning and tumor-related symptoms. Our study adds to previous findings by demonstrating the unique interplay between molecular miR-181b/d biomarkers and health related quality of life (HRQOL) score as both variables remained significant in the predictive glioma models.

Exosomes in Glioma: Unraveling Their Roles in Progression, Diagnosis, and Therapy

“…In a separate study, exosomal miR-181 emerged as a promising biomarker for early-stage human gliomas [99]. Notably, a recent study demonstrated a unique correlation between molecular miR-181b/d indicators and health-related quality of life scores, reaffirming previous findings [100]. In addition, research conducted by Fengming Lan and colleagues revealed that exosomal miR-301a exhibits potential in reflecting both cancer status and pathological variations in human glioma, positioning it as a promising candidate for diagnostic and prognostic glioma biomarkers [101].…”

Associations of miR-181a with Health-Related Quality of Life, Cognitive Functioning, and Clinical Data of Patients with Different Grade Glioma Tumors

“…Thus, it might be that relationships were lost due to the heterogeneity of the sample regarding tumor locations and other clinical characteristics. However, previous findings by our team group showed that miR-34a or miR-181b / d expression levels were related to patients’ functioning and tumor-related symptoms [ 41 , 42 ]. Therefore, we believe that current findings support the idea that levels of miR-181a expression might be valuable not only in predicting longer survival but also in better general functioning.…”

Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System

“…On the other hand, the actions of NRSF in gliomas involve microRNAs. These microRNAs include tumor-promoting miR-21, miR-10b, and miR26a, and tumor-inhibiting miR-326, miR-128, miR-181, miR-7, and miR-124a ( Fu et al, 2018 ; Huang et al, 2019 ; Bautista-Sánchez et al, 2020 ; Bhere et al, 2020 ; Rezaei et al, 2020 ; Stakaitis et al, 2020 ; Wang et al, 2020 ). For example, high NRSF expression in glioblastoma decreases the miR-124a expression, and thereby increasing the expression of NRSF-target genes, such as SNAI-1 (a transcription factor that promotes cell invasion and tumor metastases), Scp1, and PTPN12 (two small phosphatases), and finally stimulating cell proliferation ( Tivnan et al, 2014 ).…”