Zhao Dunmei, Liu Honggang, Liu Huachao, Zhang Xueqing, Zhang Meng, Kolluri Vijay Kumar, Feng Xulong, He Zhenglei, Wang Minghua, Zhu Ting'an, Yan Xiaolong, Zhou Yinghui
Department of Biochemistry and Molecular Biology, Medical College, Soochow University Suzhou, China.
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University Xi'an, China.
Am J Transl Res. 2020 Jan 15;12(1):162-170. eCollection 2020.
Circular RNAs (circRNAs) represent a class of endogenous non-coding RNAs. Recently, it has been reported that circRNAs might serve as novel potential biomarkers for the diagnosis of cancer, including non-small cell lung cancer (NSCLC). Mutations in the ATP binding cassette subfamily A member 3 () have been increasingly associated with lung disease; however, roles for circRNAs at the locus have not been identified. To characterize novel biomarkers in NSCLC, a bioinformatics platform was used to select circRNAs within the gene. Divergent primers were designed for hsa_circ_0037515 and hsa_circ_0037516, and the PCR products were sequenced to verify their existence in lung tissue. To evaluate diagnostic potential, expression levels of hsa_circ_0037515, hsa_circ_0037516, and were measured by quantitative reverse transcription-polymerase chain reaction; differences in expression levels were analyzed using the paired t-test, and receiver operating characteristic (ROC) curves were established. Our results demonstrate that mRNA, hsa_circ_0037515, and hsa_circ_0037516 are significantly downregulated in 61 paired samples of NSCLC compared to adjacent lung tissues (P < 0.01), and that the areas under the ROC curves for the two circRNAs (0.81 and 0.82, respectively) are indicative of diagnostic value. Furthermore, the significance was improved by considering the two circRNAs in combination (area under the ROC curve, 0.90). Our results suggest that hsa_circ_0037515 and hsa_circ_0037516 serve as novel potential biomarkers for the diagnosis of NSCLC.
环状RNA（circRNAs）是一类内源性非编码RNA。最近，有报道称circRNAs可能作为新型潜在生物标志物用于癌症诊断，包括非小细胞肺癌（NSCLC）。ATP结合盒亚家族A成员3（）的突变与肺部疾病的关联日益增加；然而，circRNAs在该位点的作用尚未明确。为了鉴定NSCLC中的新型生物标志物，利用生物信息学平台在该基因内选择circRNAs。针对hsa_circ_0037515和hsa_circ_0037516设计了发散引物，并对PCR产物进行测序以验证它们在肺组织中的存在。为了评估诊断潜力，通过定量逆转录-聚合酶链反应测量hsa_circ_0037515、hsa_circ_0037516和的表达水平；使用配对t检验分析表达水平的差异，并建立受试者工作特征（ROC）曲线。我们的结果表明，与相邻肺组织相比，在61对NSCLC样本中，mRNA、hsa_circ_0037515和hsa_circ_0037516显著下调（P < 0.01），并且这两种circRNAs的ROC曲线下面积（分别为0.81和0.82）表明具有诊断价值。此外，将这两种circRNAs结合考虑时，其诊断意义得到提高（ROC曲线下面积为0.90）。我们的结果表明，hsa_circ_0037515和hsa_circ_0037516可作为NSCLC诊断的新型潜在生物标志物。
