Zhang Ruolan, Liu Jianlin, Yang Hang, Tan Jinsong, Xiong Rong, Liu Yun, Feng Gang, Song Guiqin, Liu Kang
Institute of Tissue Engineering and Stem Cells, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, Nanchong 63700, China.
Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, China.
Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241295313. doi: 10.1177/15330338241295313.
A clinical challenge in esophageal squamous cell carcinoma (ESCC) remains the lack of applicable plasma biomarkers for screening and diagnosis. Circular RNAs (circRNAs) hold great potential as biomarkers for cancer. The study aims to explore a circRNA as a potential plasma biomarker for screening strategies and diagnostic approaches to ESCC.
Upregulated circRNAs were identified through RNA sequencing, with circCYP24A1 being identified as the target circRNA. Fluorescence in situ hybridization was employed to detect the expression of circCYP24A1 in ESCC tissue microarrays, aiming to assess the expression of circCYP24A1 in a large population and its correlation with clinical indicators. Subsequently, qRT-PCR analysis was performed on plasma samples from both ESCC patients and healthy controls to evaluate the expression levels of circCYP24A1, exploring its potential as a biomarker. Finally, the functions of circCYP24A1 were validated through CCK-8 assay, wound healing assay, trans-well assays and western blot assays.
CircCYP24A1 demonstrated upregulation in both plasma and tissues, exhibiting correlations with lymph node metastasis, TNM staging, and prognosis in ESCC. The circCYP24A1 achieved a perfect area under the curve of 0.94 for the diagnosis of ESCC, and an area under the curve of 0.76 for the prediction of lymph node metastasis. Furthermore, functional loss assays revealed that circCYP24A1 effectively promotes the epithelial-mesenchymal transition and tumor metastasis in vitro.
CircCYP24A1 emerges as a potential plasma diagnostic biomarker and a predictive factor for LNM for ESCC.
食管鳞状细胞癌(ESCC)的一项临床挑战仍然是缺乏适用于筛查和诊断的血浆生物标志物。环状RNA(circRNA)作为癌症生物标志物具有巨大潜力。本研究旨在探索一种circRNA作为ESCC筛查策略和诊断方法的潜在血浆生物标志物。
通过RNA测序鉴定上调的circRNA,circCYP24A1被确定为目标circRNA。采用荧光原位杂交检测circCYP24A1在ESCC组织微阵列中的表达,旨在评估circCYP24A1在大量人群中的表达及其与临床指标的相关性。随后,对ESCC患者和健康对照的血浆样本进行qRT-PCR分析,以评估circCYP24A1的表达水平,探索其作为生物标志物的潜力。最后,通过CCK-8测定、伤口愈合测定、Transwell测定和蛋白质免疫印迹测定验证circCYP24A1的功能。
CircCYP24A1在血浆和组织中均呈上调,与ESCC的淋巴结转移、TNM分期和预后相关。CircCYP24A1诊断ESCC的曲线下面积达到完美的0.94,预测淋巴结转移的曲线下面积为0.76。此外,功能缺失实验表明,circCYP24A1在体外可有效促进上皮-间质转化和肿瘤转移。
CircCYP24A1是ESCC潜在的血浆诊断生物标志物和LNM的预测因子。