Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, PR China.
Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, PR China.
Int J Biol Sci. 2018 Sep 1;14(11):1513-1520. doi: 10.7150/ijbs.27523. eCollection 2018.
Chemo-resistance and lung metastasis have been the two obstacles in the osteosarcoma (OS) treatment, which is still lack of effective biomarkers for prediction, diagnosis and treatment. Circular RNA (circRNA) is a new type of endogenous noncoding RNA that could serve as ideal biomarkers in cancer because of its stable loop structure. However, little is known about the diagnostic value of circRNAs in OS as well as their associations with clinicopathologic characteristics of OS patients. In the current study, we identified a novel circRNA, hsa_circ_0081001, screened by the RNA sequencing in the three paired chemo-resistant and chemo-sensitive OS cell lines (MG63/DXR vs MG63, KHOS/DXR vs KHOS, U2OS/DXR vs U2OS), and found that hsa_circ_0081001 was significantly up-regulated in the OS cell lines, tissues and serums, associated with poor overall survival and cox multivariate analysis showed that hsa_circ_0081001 was a novel independent prognostic factor for OS patients. Then, receiver operating characteristic (ROC) curve analysis revealed that hsa_circ_0081001 could act as a biomarker for the OS diagnosis and prognosis prediction, better than alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). In addition, we preliminarily found that hsa_circ_0081001 expression level may dynamically monitor and reflect the condition changes of OS patients in a small-scale prospective clinical pretest. In conclusion, our study suggested that circulating hsa_circ_0081001 could serve as a potential biomarker and therapeutic target for OS patients.
化疗耐药和肺转移一直是骨肉瘤（OS）治疗的两大障碍，目前仍然缺乏有效的预测、诊断和治疗生物标志物。环状 RNA（circRNA）是一种新型的内源性非编码 RNA，由于其稳定的环结构，可作为癌症的理想生物标志物。然而，circRNA 在骨肉瘤中的诊断价值及其与骨肉瘤患者临床病理特征的关系知之甚少。在本研究中，我们通过三对化疗耐药和化疗敏感骨肉瘤细胞系（MG63/DXR 与 MG63、KHOS/DXR 与 KHOS、U2OS/DXR 与 U2OS）的 RNA 测序筛选出一种新型 circRNA，hsa_circ_0081001，发现 hsa_circ_0081001 在骨肉瘤细胞系、组织和血清中显著上调，与总生存期不良相关，cox 多因素分析显示 hsa_circ_0081001 是骨肉瘤患者的一个新的独立预后因素。然后，受试者工作特征（ROC）曲线分析显示 hsa_circ_0081001 可作为骨肉瘤诊断和预后预测的生物标志物，优于碱性磷酸酶（ALP）和乳酸脱氢酶（LDH）。此外，我们初步发现 hsa_circ_0081001 的表达水平可能在小范围前瞻性临床预测试中动态监测和反映骨肉瘤患者的病情变化。总之，本研究表明，循环 hsa_circ_0081001 可作为骨肉瘤患者的潜在生物标志物和治疗靶点。
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