Kang Yanli, You Jianbin, Gan Yuhan, Chen Qianshun, Huang Chen, Chen Falin, Xu Xunyu, Chen Liangyuan
Department of Clinical Laboratory, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Department of Thoracic Surgery, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Front Oncol. 2022 Jun 7;12:912246. doi: 10.3389/fonc.2022.912246. eCollection 2022.
Circular RNAs (circRNAs) play an important role in tumorigenesis and several circulating circRNA signatures are closely associated with tumor diagnosis. However, the expression and clinical significance of the two forms of circulating circRNAs, serum and serum exosomal, in patients with lung adenocarcinoma (LUAD), have not been characterized.
Three differentially expressed exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were selected based on previous exosomal circRNA sequencing data analyses of LUAD patients. The expression of these circRNAs in serum and serum-derived exosomes of LUAD patients was assessed using quantitative real-time PCR (qRT-PCR), and correlations between circRNA expression and clinicopathological characteristics were analyzed. The reliability of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 to diagnose LUAD was evaluated using receiver operating characteristic (ROC) analysis.
Expression of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 were significantly higher in LUAD patients than in healthy donors, and significantly lower after surgery. These three serum exosomal circRNAs were also associated with a higher cancer stage. Exosomal hsa_circ_0001492 expression was positively correlated with carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) levels. An association between the expression of the three serum circRNAs and clinical characteristics was not observed. In addition, the three serum exosomal circRNAs had higher diagnostic sensitivity and specificity than the serum circRNAs, and the area under the curve (AUC) of all three serum exosomal circRNAs was >0.75. The combination of exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 had better diagnostic sensitivity and specificity than that of a single marker, with an AUC value of 0.805.
The serum and serum exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were upregulated in LUAD patients. Serum exosomal circRNAs may serve as more effective biomarkers than serum circRNAs for LUAD diagnosis and may further aid the detection of this disease.
环状RNA（circRNAs）在肿瘤发生中起重要作用，几种循环circRNA特征与肿瘤诊断密切相关。然而，肺腺癌（LUAD）患者中血清和血清外泌体这两种形式的循环circRNAs的表达及临床意义尚未明确。
基于先前对LUAD患者的外泌体circRNA测序数据分析，选择了三种差异表达的外泌体circRNAs，即hsa_circ_0001492、hsa_circ_0001439和hsa_circ_0000896。使用定量实时PCR（qRT-PCR）评估这些circRNAs在LUAD患者血清和血清来源外泌体中的表达，并分析circRNA表达与临床病理特征之间的相关性。使用受试者工作特征（ROC）分析评估血清和血清外泌体hsa_circ_0001492、hsa_circ_0001439和hsa_circ_0000896诊断LUAD的可靠性。
LUAD患者血清和血清外泌体中hsa_circ_0001492、hsa_circ_0001439和hsa_circ_0000896的表达显著高于健康供体，术后显著降低。这三种血清外泌体circRNAs也与更高的癌症分期相关。外泌体hsa_circ_0001492表达与癌胚抗原（CEA）和神经元特异性烯醇化酶（NSE）水平呈正相关。未观察到三种血清circRNAs的表达与临床特征之间的关联。此外，三种血清外泌体circRNAs比血清circRNAs具有更高的诊断敏感性和特异性，并且所有三种血清外泌体circRNAs的曲线下面积（AUC）均>0.75。外泌体hsa_circ_0001492、hsa_circ_0001439和hsa_circ_0000896的组合比单一标志物具有更好的诊断敏感性和特异性，AUC值为0.805。
LUAD患者血清和血清外泌体circRNAs，即hsa_circ_0001492、hsa_circ_0001439和hsa_circ_0000896上调。血清外泌体circRNAs可能比血清circRNAs作为LUAD诊断的更有效生物标志物，并可能进一步有助于该疾病的检测。
