Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 1111 Wenzhou Avenue, Longwan District, Wenzhou, Zhejiang, 325024, China.
Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325036, China.
BMC Cancer. 2024 Sep 20;24(1):1172. doi: 10.1186/s12885-024-12943-x.
In the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML patients at risk for progression are limited. This study explored whether essential circular RNAs (circRNAs) can be used as biomarkers for diagnosing and monitoring CML disease progression and assessing CML prognosis.
Peripheral blood (PB) samples were collected from 173 CML patients (138 patients with chronic phase CML [CML-CP] and 35 patients with accelerated phase/blast phase CML [CML-AP/BP]) and 63 healthy controls (HCs). High-throughput RNA sequencing (RNA-Seq) was used to screen dysregulated candidate circRNAs for a circRNA signature associated with CML disease progression. Quantitative real-time PCR (qRT-PCR) was used for preliminary verification and screening of candidate dysregulated genes, as well as subsequent exploration of clinical applications. Receiver operating characteristic (ROC) curve analysis, Spearman's rho correlation test, and the Kaplan-Meier method were used for statistical analysis.
The aberrant expression of hsa_circ_0006010 and hsa_circ_0002903 during CML progression could serve as valuable biomarkers for differentiating CML-AP/BP patients from CMP-CP patients or HCs. In addition, the expression levels of hsa_circ_0006010 and hsa_circ_0002903 were significantly associated with the clinical features of CML patients but were not directly related to the four scoring systems. Furthermore, survival analysis revealed that high hsa_circ_0006010 expression and low hsa_circ_0002903 expression indicated poor progression-free survival (PFS) in CML patients. Finally, PB hsa_circ_0006010 and hsa_circ_0002903 expression at diagnosis may also serve as disease progression surveillance markers for CML patients but were not correlated with PB BCR-ABL1/ABL1.
Our study demonstrated that PB levels of hsa_circ_0006010 and hsa_circ_0002903 may serve as novel diagnostic, surveillance, and prognostic biomarkers for CML disease progression and may contribute to assisting in the diagnosis of CML patients at risk for progression and accurate management of advanced CML patients.
在酪氨酸激酶抑制剂（TKI）治疗时代，慢性髓性白血病（CML）的进展仍然是一个重大的临床挑战，用于早期识别有进展风险的 CML 患者的遗传生物标志物有限。本研究探讨了是否可以将必需的环状 RNA（circRNA）用作诊断和监测 CML 疾病进展以及评估 CML 预后的生物标志物。
收集了 173 名 CML 患者（138 名慢性期 CML [CML-CP]患者和 35 名加速期/急变期 CML [CML-AP/BP]患者）和 63 名健康对照者（HCs）的外周血（PB）样本。采用高通量 RNA 测序（RNA-Seq）筛选与 CML 疾病进展相关的差异表达候选 circRNA，构建 circRNA 特征用于 CML 疾病进展。采用实时定量 PCR（qRT-PCR）进行候选差异表达基因的初步验证和筛选，以及后续临床应用的探索。采用受试者工作特征（ROC）曲线分析、斯皮尔曼 rho 相关检验和 Kaplan-Meier 方法进行统计分析。
在 CML 进展过程中 hsa_circ_0006010 和 hsa_circ_0002903 的异常表达可作为区分 CML-AP/BP 患者与 CML-CP 患者或 HCs 的有价值的生物标志物。此外，hsa_circ_0006010 和 hsa_circ_0002903 的表达水平与 CML 患者的临床特征显著相关，但与四个评分系统无关。此外，生存分析显示，CML 患者高 hsa_circ_0006010 表达和低 hsa_circ_0002903 表达预示着无进展生存（PFS）不良。最后，CML 患者诊断时 PB hsa_circ_0006010 和 hsa_circ_0002903 的表达也可作为疾病进展监测标志物，但与 PB BCR-ABL1/ABL1 无关。
本研究表明，PB hsa_circ_0006010 和 hsa_circ_0002903 的水平可能作为 CML 疾病进展的新型诊断、监测和预后生物标志物，有助于辅助诊断有进展风险的 CML 患者，并对 CML 高危患者的准确管理提供帮助。
