Yu Yunhe, Zheng Wenfang, Ji Changle, Wang Xuehui, Chen Mingkuan, Hua Kaiyao, Deng Xiaochong, Fang Lin
Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
School of Medicine, Tongji University, Shanghai, China.
Front Pharmacol. 2022 Feb 15;13:811856. doi: 10.3389/fphar.2022.811856. eCollection 2022.
Early diagnosis is the key to improving the prognosis of breast cancer (BC) patients; however, there are currently no circulating biomarkers that demonstrate good sensitivity and specificity. This study applied circular RNA (circRNA) microarray analysis, screening, and verification in BC plasma samples to identify three tumor-derived differentially expressed circRNAs: hsa_circ_0000091, hsa_circ_0067772, and hsa_circ_0000512. We constructed a diagnostic model using logistic regression analysis in the training set and established an optimal diagnostic model based on the three circRNAs, which showed sensitivity, specificity, and area under the curve (AUC) values of .971, .902, and .974, respectively. We then verified the diagnostic model in the test set which showed satisfactory stability for BC diagnosis. Additionally, the expression of hsa_circ_0000091 in plasma correlated with axillary lymph node (ALN) metastasis, TNM stage, and prognosis of BC patients. Furthermore, hsa_circ_0000091 combined with ultrasound showed predictive ability for ALN metastasis, with an AUC of .808. These findings suggested that the three identified circRNAs can be used as circulating biomarkers for BC diagnosis, with hsa_circ_0000091 potentially representing a prognostic biomarker for BC and novel approach for predicting ALN metastasis.
早期诊断是改善乳腺癌(BC)患者预后的关键;然而,目前尚无具有良好敏感性和特异性的循环生物标志物。本研究对BC血浆样本进行环状RNA(circRNA)微阵列分析、筛选及验证,以鉴定出三种肿瘤来源的差异表达circRNA:hsa_circ_0000091、hsa_circ_0067772和hsa_circ_0000512。我们在训练集中使用逻辑回归分析构建了诊断模型,并基于这三种circRNA建立了最佳诊断模型,其敏感性、特异性和曲线下面积(AUC)值分别为0.971、0.902和0.974。然后我们在测试集中验证了该诊断模型,其对BC诊断显示出令人满意的稳定性。此外,血浆中hsa_circ_0000091的表达与BC患者的腋窝淋巴结(ALN)转移、TNM分期及预后相关。此外,hsa_circ_0000091联合超声对ALN转移具有预测能力,AUC为0.808。这些发现表明,所鉴定的三种circRNA可作为BC诊断的循环生物标志物,其中hsa_circ_0000091可能代表BC的一种预后生物标志物以及预测ALN转移的新方法。