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探索用于改善肾细胞癌检测的尿液环状RNA生物标志物

Investigating Urinary Circular RNA Biomarkers for Improved Detection of Renal Cell Carcinoma.

作者信息

Peter Madonna R, Zhao Fang, Jeyapala Renu, Kamdar Shivani, Xu Wei, Hawkins Cynthia, Evans Andrew J, Fleshner Neil E, Finelli Antonio, Bapat Bharati

机构信息

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.

Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.

出版信息

Front Oncol. 2022 Jan 31;11:814228. doi: 10.3389/fonc.2021.814228. eCollection 2021.

Abstract

Renal cell carcinomas (RCC) are usually asymptomatic until late stages, posing several challenges for early detection of malignant disease. Non-invasive liquid biopsy biomarkers are emerging as an important diagnostic tool which could aid with routine screening of RCCs. Circular RNAs (circRNAs) are novel non-coding RNAs that play diverse roles in carcinogenesis. They are promising biomarkers due to their stability and ease of detection in small quantities from non-invasive sources such as urine. In this study, we analyzed the expression of various circRNAs that were previously identified in RCC tumors (circEGLN3, circABCB10, circSOD2 and circACAD11) in urinary sediment samples from non-neoplastic controls, patients with benign renal tumors, and clear cell RCC (ccRCC) patients. We observed significantly reduced levels of circEGLN3 and circSOD2 in urine from ccRCC patients compared to healthy controls. We also assessed the linear variant of EGLN3 and found differential expression between patients with benign tumors compared to ccRCC patients. These findings highlight the potential of circRNA markers as non-invasive diagnostic tools to detect malignant RCC.

摘要

肾细胞癌(RCC)通常在晚期才出现症状,这给恶性疾病的早期检测带来了诸多挑战。非侵入性液体活检生物标志物正成为一种重要的诊断工具,可辅助肾细胞癌的常规筛查。环状RNA(circRNAs)是新型非编码RNA,在肿瘤发生中发挥多种作用。由于其稳定性以及能够从尿液等非侵入性来源中轻松检测到少量样本,它们有望成为生物标志物。在本研究中,我们分析了先前在肾细胞癌肿瘤中鉴定出的各种环状RNA(circEGLN3、circABCB10、circSOD2和circACAD11)在非肿瘤对照、良性肾肿瘤患者以及透明细胞肾细胞癌(ccRCC)患者的尿沉渣样本中的表达情况。我们观察到,与健康对照相比,ccRCC患者尿液中circEGLN3和circSOD2的水平显著降低。我们还评估了EGLN3的线性变体,发现良性肿瘤患者与ccRCC患者之间存在差异表达。这些发现凸显了环状RNA标志物作为检测恶性肾细胞癌的非侵入性诊断工具的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c7/8841801/3b9b75b9c16c/fonc-11-814228-g001.jpg

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