Lu Guo-Jun, Cui Jian, Qian Qian, Hou Zhi-Bo, Xie Hai-Yan, Hu Wei, Hao Ke-Ke, Xia Ning, Zhang Yu
Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, People's Republic of China.
Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
Onco Targets Ther. 2020 Oct 23;13:10775-10783. doi: 10.2147/OTT.S274932. eCollection 2020.
Circular RNAs (circRNAs) play important roles in tumorigenesis, including lung cancer. However, the expression profile and clinical value of circRNAs in lung adenocarcinoma remain unclear. The purpose of this study was to establish the circRNAs expression profile of lung adenocarcinoma and determine its potential diagnostic and prognostic value.
The global expression profile of circRNAs in lung adenocarcinoma tissue was determined from five paired lung adenocarcinoma tissues and adjacent normal tissues. The expression levels of selected candidate circRNA were validated by qRT-PCR. Sequence analysis was used to confirm the specificity of amplified circRNA. The candidate circRNA level was further detected in plasma samples from lung adenocarcinoma patients and healthy controls. The relationships between their levels and clinicopathological factors were explored. Receiver operating characteristic (ROC) curve was constructed to differentiate lung adenocarcinoma from healthy controls. Kaplan-Meier was performed to show survival curves and survival characteristics. The significance of different prognostic factors for overall survival (OS) was analyzed using Cox proportional hazards model.
CircRNA microarray showed 394 circRNAs were differentially expressed, including 215 up-regulated and 179 down-regulated circRNAs. Hsa_circ_0001715 was the most up-regulated circRNA in lung adenocarcinoma tissues. Plasma hsa_circ_0001715 levels were significantly higher in lung adenocarcinoma patients versus healthy controls ( < 0.001). We further found that high plasma hsa_circ_0001715 was significantly correlated with TNM stage ( = 0.039) and distant metastasis ( = 0.030). Furthermore, ROC curve analysis showed that hsa_circ_0001715 had high diagnostic value, and the area under the curve (AUC) was 0.871. Lung adenocarcinoma patients with plasma hsa_circ_0001715 levels over 0.417 had significantly shorter OS than those with lower levels ( = 0.004). Univariate and multivariate survival analysis showed that plasma hsa_circ_0001715 level was an independent prognostic factor for the OS.
Our study revealed an aberrant circRNA expression profile in lung adenocarcinoma, and hsa_circ_0001715 is up-regulated and could act as a novel diagnostic and prognostic biomarker for lung adenocarcinoma.
环状RNA（circRNAs）在包括肺癌在内的肿瘤发生过程中发挥重要作用。然而，circRNAs在肺腺癌中的表达谱及临床价值仍不清楚。本研究的目的是建立肺腺癌的circRNAs表达谱，并确定其潜在的诊断和预后价值。
从五对肺腺癌组织及相邻正常组织中确定肺腺癌组织中circRNAs的整体表达谱。通过qRT-PCR验证所选候选circRNA的表达水平。采用序列分析确认扩增的circRNA的特异性。在肺腺癌患者和健康对照者的血浆样本中进一步检测候选circRNA水平。探讨其水平与临床病理因素之间的关系。构建受试者工作特征（ROC）曲线以区分肺腺癌与健康对照者。采用Kaplan-Meier法绘制生存曲线并显示生存特征。使用Cox比例风险模型分析不同预后因素对总生存期（OS）的意义。
circRNA微阵列显示394个circRNAs差异表达，其中215个上调，179个下调。Hsa_circ_0001715是肺腺癌组织中上调最明显的circRNA。肺腺癌患者血浆中hsa_circ_0001715水平显著高于健康对照者（<0.001）。我们进一步发现，血浆hsa_circ_0001715水平高与TNM分期（=0.039）和远处转移（=0.030）显著相关。此外，ROC曲线分析显示hsa_circ_0001715具有较高的诊断价值，曲线下面积（AUC）为0.871。血浆hsa_circ_0001715水平超过0.417的肺腺癌患者的OS明显短于水平较低者（=0.004）。单因素和多因素生存分析显示，血浆hsa_circ_0001715水平是OS的独立预后因素。
我们的研究揭示了肺腺癌中异常的circRNA表达谱，hsa_circ_0001715上调，可作为肺腺癌新的诊断和预后生物标志物。
