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循环 miR-146a 表达作为急性淋巴细胞白血病的非侵入性预测生物标志物。

Circulating miR-146a expression as a non-invasive predictive biomarker for acute lymphoblastic leukemia.

机构信息

School of Biochemistry and Biotechnology, University of the Punjab, Lahore, 54590, Pakistan.

Institute of Molecular Biology & Biotechnology, The University of Lahore, Lahore, Pakistan.

出版信息

Sci Rep. 2021 Nov 23;11(1):22783. doi: 10.1038/s41598-021-02257-4.

Abstract

Dysregulation of non-coding microRNAs during the course of tumor development, invasion and/or progression to the distant organs, makes them a promising candidate marker for the diagnosis of cancer and associated malignancies. This exploratory study aims at evaluating the usefulness of plasma concentration of circulating mir-146a as a non-invasive biomarker for acute lymphoblastic leukemia (ALL). Total RNA including miRNA was isolated from 110 plasma samples of patients (n = 66), healthy controls (n = 24) and follow up (n = 20) cases and reverse transcribed. Relative concentrations were assessed using real-time quantitative PCR and fold-change was calculated by 2 method. Finally, relative concentrations were correlated to clinicopathological factors. Patients (n = 66) were analyzed to determine fold expression of miR-146a in plasma samples of ALL. Before chemotherapy, pediatric (n = 42) and adult (n = 24) showed overexpression of miR-146a compared with healthy controls (P < 0.0001). There was no effect of age and gender on mir-146a expression in plasma. mirR-146a expression was independent of clinical and hematological features. Moreover, miR-146a levels in plasma of paired samples (n = 20) after treatment showed significant decrease in expression (P < 0.001). Expression of plasma miR-146a may be utilized as non-invasive marker to diagnose and predict prognosis in pediatric and adult patients with ALL. Moreover predicted targets may be utilized for ALL therapy in future.

摘要

在肿瘤发展、侵袭和/或转移到远处器官的过程中,非编码 microRNA 的失调使其成为癌症及相关恶性肿瘤诊断的有希望的候选标志物。本探索性研究旨在评估循环 mir-146a 血浆浓度作为急性淋巴细胞白血病 (ALL) 非侵入性生物标志物的有用性。从 110 例患者(n=66)、健康对照者(n=24)和随访者(n=20)的 110 份血浆样本中分离总 RNA 包括 miRNA,并进行逆转录。使用实时定量 PCR 评估相对浓度,并通过 2 法计算 fold-change。最后,相对浓度与临床病理因素相关。分析患者(n=66)以确定 ALL 血浆样本中 miR-146a 的 fold 表达。在化疗前,儿科患者(n=42)和成人患者(n=24)与健康对照者相比,miR-146a 表达过度(P<0.0001)。年龄和性别对血浆中 mir-146a 的表达没有影响。mirR-146a 表达与临床和血液学特征无关。此外,治疗后配对样本(n=20)的血浆 miR-146a 水平表达显著降低(P<0.001)。血浆 miR-146a 的表达可作为诊断和预测儿科和成人 ALL 患者预后的非侵入性标志物。此外,预测靶点可用于未来的 ALL 治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e447/8611079/b0ad7803d161/41598_2021_2257_Fig1_HTML.jpg

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