Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations

Qu, Kai; Lin, Ting; Pang, Qing; Liu, Tian; Wang, Zhixin; Tai, Ming-Hui; Fang, Meng; Zhang, Jingyao; Wan, Yong; Mao, Ping; Dong, Xiaoqun; Liu, Chang; Niu, Wenquan; Dong, Shunbin

doi:10.18632/oncotarget.9188

Cited by 49 publications

(37 citation statements)

References 88 publications

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“…There are many factors affecting the prognoses of glioma patients. In analyzing the relationship between miR-21 and prognosis, it is important to consider confounding effects caused by the degree of malignancy as well as other factors [23][24][25][26][27][28][29][30][31] . In this meta-analysis, five included studies used a multivariate Cox regression analysis to study the relationship between miR-21 expression and OS, and in each of these five studies, the covariate confounding effect was adjusted by performing a multivariate Cox regression analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpressions of miR-21, also known as oncomiR, has been reported in various cancers, including gliomas [19][20][21][22] . Previous studies have shown that overexpression of miR-21 is associated with poor survival of glioma patients [23][24][25][26][27][28][29] . However, two studies reported insignificant correlations between miR-21 and prognosis in glioma patients 30,31 .…”

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confidence: 99%

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Prognostic value of miR-21 in gliomas: comprehensive study based on meta-analysis and TCGA dataset validation

Jiang

Liu

et al. 2020

Sci Rep

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Recent studies have highlighted the value of microRNA-21 (miR-21) as a prognostic biomarker in gliomas. However, the role of miR-21 in predicting prognosis remains controversial. We performed a comprehensive study based upon a meta-analysis and The Cancer Genome Atlas (TCGA) glioma dataset validation to clarify the prognostic significance of miR-21 in glioma patients. In this study, we searched Embase, PubMed, Web of science, CNKI, SinoMed, and Wanfang databases for records up to May 2018. Relevant data were extracted to assess the correlation between miR-21 expression and survival in glioma patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to describe association strength. We further used multivariate Cox regression analysis to assess miR-21 expression in the TCGA glioma dataset to validate the relationship between miR-21 expression and survival. Nine studies were included in the meta-analysis. Among them, eight studies provided data on overall survival (OS) with a pooled HR of 1.91 (95% CI: 1.34, 2.73), indicating that higher expression of miR-21 was significantly associated with worse OS in glioma patients; for the other study, which provided data on progression-free survival (PFS), no statistically significant HR was reported for PFS in the glioma patients (HR = 1.23, 95% CI: 0.41, 3.72). A multivariate Cox regression analysis of the miR-21 expression in the TCGA glioma dataset revealed that overexpression of miR-21 was a potential independent prognostic biomarker of poorer OS (HR = 1.27, 95% CI: 1.01, 1.59) and poorer PFS (HR = 1.46, 95% CI: 1.17, 1.82). Our findings suggest that higher expression of miR-21 is correlated with poorer glioma prognosis. Gliomas are one of the most common central nervous system (CNS) glial neoplasms, accounting for 30% of all CNS tumors and 80% of malignant brain tumors 1 , respectively. According to the World Health Organization (WHO) classification, gliomas are classified as grade I through grade IV 2. Low-grade gliomas (LGG, grades I-II) are well-differentiated and grow slowly, while high-grade gliomas (HGG, grades III-IV) are characterized by poor differentiation and rapid progression, and the prognosis of HGG is usually poor. Grade IV glioma, known as glioblastoma multiforme (GBM), is extremely aggressive, and comprises 55.1% of all gliomas 3. Although recent progress has been made in surgical and radiotherapy techniques, the prognoses of GBM patients have not significantly improved 4,5 , and GBM remains one of the most incurable cancers 6 , with a 5-year survival rate of only 5.1% 3. Some clinical factors impact the prognosis of glioma patients, such as age at diagnosis, WHO grade,

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Prognostic value of miR-21 in gliomas: comprehensive study based on meta-analysis and TCGA dataset validation

Jiang

Liu

et al. 2020

Sci Rep

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“…MiR-21 is one of the most studied miRNAs and is overexpressed in cancer tissues. Qu et al [23] analyzed that extracellular miR-21 exhibited an outstanding diagnostic accuracy in detecting brain cancer, and this accuracy was more obvious in glioma diagnosis. Thus, combination of several miRNAs may be useful for precious prediction of glioma genesis and progression.…”

Section: Discussionmentioning

confidence: 99%

MiR‐634 sensitizes glioma cells to temozolomide by targeting CYR61 through Raf‐ERK signaling pathway

2018

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Glioma is the most common intracranial malignant tumors, accounting for about 40% of intracranial tumors. Primary or secondary drug resistance is one of the main reasons for the failure of treatment. The oncogenic or tumor‐suppressive roles of miR‐634 have been revealed in different types of cancer. However, the role of miR‐634 in glioma remains unknown and whether miR‐634 could sensitize glioma cells to temozolomide also is unclear. Here, we aim to investigate the biological function of miR‐634 and the possible mechanisms in glioma. In this study, we found that miR‐634 was downregulated in glioma tissues compared with normal brain tissues, and its expression was associated with tumor size and WHO grade. Importantly, glioma patients with low miR‐634 expression showed a shorter survival time than patients which had high expression of miR‐634. This study also showed that miR‐634 was decreased in temozolomide‐resistant glioma cells, and restoration of miR‐634 could sensitize the resistant cells to temozolomide by targeting CYR61 through Raf‐ERK signaling. Our study provides a potential target for overcome drug resistance in glioma.

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“…Recently, several studies have reported circulating miRNA as a biomarker in cancer studies by using serum, plasma and whole blood [18][19]. For instance, Qu et al demonstrated that circulating miR-21-5p had a relatively high diagnostic accuracy for the diagnosis of PC (sensitivity 0.77, specificity 0.80 and an AUC 0.78 (95% CI: 0.66-0.90)) and might be a promising diagnostic biomarker [20]. A gastric cancer study revealed that miR-19b-3p and miR-16-5p might be prospective biomarkers to detect gastric cancer and have great potential in applications for early screening and progression evaluation [21].…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-31-5p may be a potential diagnostic biomarker in nasopharyngeal carcinoma

et al. 2019

neo

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Aberrant expression of miR-31-5p has been detected in various cancers and plays a significant role in tumorigenesis. Low miR-31-5p expression was present in nasopharyngeal carcinoma (NPC) tissues and cell lines and acted as a tumor suppressive miRNA. Currently, circulating miRNAs are emerging as novel biomarkers for the early diagnosis of cancers using a non-invasive method. However, circulating miR-31-5p has rarely been reported in NPC. Therefore, the aim of this study was to explore peripheral blood miR-31-5p levels as a noninvasive biomarker and evaluate its clinical value for the early diagnosis of patients with NPC. A total of 110 participants were recruited, including 55 NPC patients and 55 healthy controls. Peripheral blood samples were collected from these participants, and total RNA was extracted to quantify the relative expression of miR-31-5p by RT-qPCR. We found a significantly lower expression of miR-31-5p in the NPC patients than in the healthy controls. Furthermore, low expression of miR-31-5p was highly correlated with tumor-node-metastasis (TNM) stage (I+II vs III+IV, p=0.001), T classification (T1 vs T2+T3+T4, p=0.036) and local lymph node metastasis (N1-N3 vs N0, p=0.002), but not distant metastasis (p=0.288). Moreover, miR-31-5p showed a moderate diagnostic performance (AUC=0.866, sensitivity = 0.782, specificity = 0.818). Thus, we concluded that circulating miR-31-5p can be a potentially novel and non-invasive biomarker for the early diagnosis of NPC and an attractive therapeutic target in NPC patients.

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Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations

Cited by 49 publications

References 88 publications

Prognostic value of miR-21 in gliomas: comprehensive study based on meta-analysis and TCGA dataset validation

Prognostic value of miR-21 in gliomas: comprehensive study based on meta-analysis and TCGA dataset validation

MiR‐634 sensitizes glioma cells to temozolomide by targeting CYR61 through Raf‐ERK signaling pathway

Circulating miR-31-5p may be a potential diagnostic biomarker in nasopharyngeal carcinoma

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