الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
 |  | from | 194 |  |  |
| | | from | 194 | | |
Abstract
In conclusion, to our knowledge, this is the first attempt to investigate circulating miRNA-21 and miRNA-181 in GBM patients, compare their expression level with that in healthy individuals as minimal invasive manner and also study their predictive prognostic role.
The over mentioned data demonstrated the efficiency of miRNA-21 and miRNA-181 in discriminating between GBM patients and control subjects with sensitivity 97% and 94% respectively, and with absolute specificity for miRNA-21 and 94% for miRNA-181. Also, the results indicated that there is a significant association between upregulation of miRNA-21, downregulation of miRNA-181, and poor OS and PFS.
Our results emphasize the clinical role of investigated miRNAs as both diagnostic and predictive prognostic markers and hence they may be used in the incoming future as therapeutic targets.
Recommendations
• Further studies on large number of samples are needed to clarify the role of TGF-β1 as an effective marker in monitoring the disease progression in GBM patients.
• Investigating the relation between the role of miRNA-21 and TGF-β1 signaling pathways in glioblastoma multiform.
• Analysis of other biomarkers in tissue samples, like proteins that are involved in glioblastoma progression signaling pathways, will be promising.
• Further investigations of the mechanisms of glioblastoma pathogenesis are needed with a deeper look for new treatment targets in novel signaling pathways that are implicated in glioblastoma progression.
Glioblastoma multiform (GBM) is the most common and aggressive form of brain cancer in adults and is universally life-threatening. Although recent progress has been made in surgical and radiotherapy techniques, the prognoses of GBM patients have not significantly improved, and GBM remains one of the most incurable cancers. Many studies have shown that biological alterations in specific genes or molecules can affect the prognosis of GBM patients. Therefore, clinical factors alone are not sufficient to assess the prognosis of patients with glioma, and more research is required to look for better prognostic biomarkers.
Circulating biomarkers are measurable biological molecules found in blood or other body fluids that provide information about a specific condition, such as cancer. Recently, many studies have revealed that miRNAs can function as oncogenes or tumor suppressors in cancer, affecting the clinical outcome. Studies have shown that miRNA expression is related to prognosis in patients with GBM, as miRNAs can be secreted into the blood, they are stable in the circulatory system, and they can be detected in plasma or serum. Therefore, miRNAs can potentially act as diagnostic and prognostic biomarkers for glioblastoma.
Thus, the aim of this study was to investigate the clinical role of two miRNAs (miRNA-21 and miRNA-181) in patients recently diagnosed with glioblastoma multiforme compared with normal subjects.
The current study was conducted on 52 subjects, classified as 32 recently diagnosed glioblastoma multiforme patients—17 males and 15 females—and 20 control subjects. The expression levels of miRNA-21 and miRNA-181 were detected in blood samples of all recruited subjects using the qRT-PCR technique. Also, the impact of the studied miRNAs on the survival analysis was detected using the Kaplan-Meier curve. Moreover, the sensitivity and specificity of the two studied miRNAs were identified using a ROC curve.
The results are summarized as follows:
• No significant difference was detected in the gender and age among the two investigated groups.
• The expression of miRNA-21 was up-regulated in GBM patients over 60 years of age with frontal masses with a tumor size > 5 cm and ECOG >2.
• MiRNA-21 expression level showed an elevated mean level in GBM patients compared to normal subjects with absolute specificity (i.e. 100%) and sensitivity of 97% with an area under the curve (AUC) of 0.971.
• The expression level of miRNA-21 was significantly reduced (P<0.01) in post treatment with fold change 100 compared to its pre-treatment levels 25.3.
• Poor progression free survival (PFS) and overall survival (OS) reported an increase in miRNA-21 expression.
• The expression of miRNA-181 was down-regulated in GBM patients over 60 years of age with frontal masses with a tumor size > 5 cm and ECOG >2.
• MiRNA-181 expression level was decreased GBM patients compared to controls, and its diagnostic efficacy showed sensitivity and specificity of 94% with an AUC of 0.94.
• Post treatment molecular analysis revealed significant elevation (P= 0.014) in the expression levels of mi-RNA-181 with fold change 30.6 compared to its pre-treatment levels 19.3.
• Poor progression free survival (PFS) and overall survival (OS) reported a decrease in miRNA-181 expression.
In conclusion, the results of this study underscore the clinical role of the studied miRNAs (miRNA-21 and miRNA-181) both as diagnostic and predictive prognostic markers and could therefore be used as therapeutic targets in the near future.
• There was a significant (p=0.007) negative correlation (r = -0.579) between miRNA-21 expression level and miRNA-181.
• A significant positive correlation (p = 0.029) (r = 0.489) was detected between the tumor size and miRNA-21.
• A significant negative correlation was detected between the tumor size and miRNA-181 with (p = 0.022), (r = -0.510)