AB060. Autophagy-associated biomarkers ULK2, UVRAG, and miRNAs miR-21, miR-126, and miR-374: prognostic significance in glioma patients.

IF 2.1 4区医学 Q3 ONCOLOGY Chinese clinical oncology Pub Date : 2024-08-01 DOI:10.21037/cco-24-ab060

Wajiha Amin, Syed Hani Abidi, Sufiyan Sufiyan, Sahar Ilyas, Sana Naeem, Siraj Uddin, Syed Ather Enam, Nouman Mughal

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Abstract

Background: Autophagy is a self-renewing process of the cell having a dual role in gliomagenesis depending on the tumor stage. Several microRNAs play a key role in the regulation of autophagy and the outcome of cancer. We investigated the potential relevance of autophagy in gliomagenesis and survival by exploring the association of the basal gene expression of autophagy-associated markers LC3, ULK1/2, UVRAG, Beclin1, mTOR, UVRAG, PI3K, AKT, PTEN and their target microRNAs miR-126, miR-374, miR-21, miR-7, miR-204 and miR-100 in low- and high-grades of gliomas.

Methods: A total of 50 fresh glioma tissues were used for the extraction of RNA using TRIzol-Chloroform method and reverse transcribed cDNA. The cDNA was used to determine the expression of genes and microRNAs using quantitative real-time polymerase chain reaction (qPCR). Mann-Whitney U-test was used to determine the statistical significance.

Results: In high-grade glioma, increased expression of AKT and miR-21, coupled with reduced ULK2 and LC3 expression was distinctly observed. While correlation analysis identified a strong positive correlation between ULK2 and UVRAG, PTEN, miR-7, and miR-100 and a moderate positive correlation emerged between ULK2 and mTOR, miR-7, miR-30, miR-100, miR-204, and miR-374, also between miR-21 and miR-126 in low-grade glioma. Similarly, a positive correlation appeared between ULK2 and AKT, LC3, PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, miR-7 and miR-374. AKT positively correlated with LC3, PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, miR-7, miR-30, miR-204, miR-374, miR-126 and miR-21 weakly correlated with AKT and miR-30 in high-grade glioma. The low ULK2, UVRAG, and miR-374 expression group exhibited significantly poor overall survival in glioma, while miR-21 over-expression indicated a poor prognosis in glioma patients.

Conclusions: This study provides comprehensive insights into the molecular landscape of gliomas, highlighting the dysregulation of autophagy genes ULK2, and UVRAG and the associated miR-21, miR-126 and miR-374 as potential prognostic biomarkers and emphasizing their unique significance in shaping survival outcomes in gliomas patients.

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AB060.自噬相关生物标志物 ULK2、UVRAG 和 miRNAs miR-21、miR-126 和 miR-374：在胶质瘤患者中的预后意义。

背景：自噬是细胞的自我更新过程，在胶质瘤的发生过程中具有双重作用，这取决于肿瘤的阶段。一些微RNA在自噬的调控和癌症的结局中起着关键作用。我们通过探讨自噬相关标志物 LC3、ULK1/2、UVRAG、Beclin1、mTOR、UVRAG、PI3K、AKT、PTEN 的基础基因表达与它们在低度和高度胶质瘤中的靶标 microRNAs miR-126、miR-374、miR-21、miR-7、miR-204 和 miR-100 的关系，研究了自噬在胶质瘤发生和生存中的潜在相关性：采用 TRIzol-Cloroform 法提取 50 个新鲜胶质瘤组织的 RNA，并反转录 cDNA。使用实时定量聚合酶链反应（qPCR）测定 cDNA 中基因和 microRNA 的表达。采用 Mann-Whitney U 检验确定统计学意义：结果：在高级别胶质瘤中，明显观察到 AKT 和 miR-21 表达增加，ULK2 和 LC3 表达减少。相关性分析发现，在低级别胶质瘤中，ULK2 与 UVRAG、PTEN、miR-7 和 miR-100 呈强正相关，ULK2 与 mTOR、miR-7、miR-30、miR-100、miR-204 和 miR-374 呈中度正相关，miR-21 与 miR-126 也呈正相关。同样，ULK2 与 AKT、LC3、PI3K、PTEN、ULK1、VPS34、mTOR、Beclin1、UVRAG、miR-7 和 miR-374 呈正相关。在高级别胶质瘤中，AKT与LC3、PI3K、PTEN、ULK1、VPS34、mTOR、Beclin1、UVRAG、miR-7、miR-30、miR-204、miR-374、miR-126和miR-21呈正相关，与AKT和miR-30呈弱相关。低ULK2、UVRAG和miR-374表达组的胶质瘤患者总生存率明显较低，而miR-21过度表达则表明胶质瘤患者预后较差：这项研究全面揭示了胶质瘤的分子图谱，强调了自噬基因ULK2和UVRAG的失调以及相关的miR-21、miR-126和miR-374是潜在的预后生物标志物，并强调了它们在影响胶质瘤患者生存结果方面的独特意义。

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来源期刊

Chinese clinical oncology ONCOLOGY-

CiteScore

3.90

自引率

0.00%

发文量

期刊介绍： The Chinese Clinical Oncology (Print ISSN 2304-3865; Online ISSN 2304-3873; Chin Clin Oncol; CCO) publishes articles that describe new findings in the field of oncology, and provides current and practical information on diagnosis, prevention and clinical investigations of cancer. Specific areas of interest include, but are not limited to: multimodality therapy, biomarkers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to cancer. The aim of the Journal is to provide a forum for the dissemination of original research articles as well as review articles in all areas related to cancer. It is an international, peer-reviewed journal with a focus on cutting-edge findings in this rapidly changing field. To that end, Chin Clin Oncol is dedicated to translating the latest research developments into best multimodality practice. The journal features a distinguished editorial board, which brings together a team of highly experienced specialists in cancer treatment and research. The diverse experience of the board members allows our editorial panel to lend their expertise to a broad spectrum of cancer subjects.