基于芯片分析和 RT-qPCR 验证的儿童急性髓系白血病疾病风险和治疗反应预测的环状 RNA 筛选和验证。
Screening and validating circular RNAs that estimate disease risk and treatment response of pediatric acute myeloid leukemia: a microarray-based analyses and RT-qPCR validation.
机构信息
Department of Pediatrics, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, China.
出版信息
J Cancer Res Clin Oncol. 2023 Oct;149(13):11233-11245. doi: 10.1007/s00432-023-04879-9. Epub 2023 Jun 26.
PURPOSE
Circular RNA (circRNA) is a type of novel non-coding RNA with close involvement in the tumorigenesis and treatment response of leukemias. This study aimed to screen and validate candidate circRNAs that estimate disease risk and response to induction therapy of pediatric acute myeloid leukemia (AML).
METHODS
Bone marrow samples were obtained from 4 complete response (CR) pediatric AML patients, 4 non-CR pediatric AML patients, and 4 controls to screen differentially expressed circRNAs (DECs) through microarray analyses. Ten candidate circRNAs were selected and validated in 40 pediatric AML patients and 10 controls through reverse transcription-quantitative polymerase chain reaction.
RESULTS
Microarray assay discovered 378 upregulated DECs and 688 downregulated DECs in pediatric AML patients vs. controls; 832 upregulated DECs and 950 downregulated DECs in CR AML patients vs. non-CR AML patients. Then cross-analysis identified 441 DECs that both related to pediatric AML risk and CR achievement. Further validation of ten candidate circRNAs in larger sample-sized populations showed that circ_0032891, circ_0076995, circ_0014352, circ_0047663, circ_0007444, circ_0001684, circ_0000544, and circ_0005354 were related to pediatric AML risk; circ_0032891, circ_0076995, circ_0014352, circ_0047663, circ_0007444, circ_0001684, and circ_0000544 were related to CR achievement in pediatric AML patients. Regarding the correlation of candidate circRNAs with survival profile, only circ_0032891, circ_0076995, and circ_0000544 forecasted event-free survival; circ_0076995 and circ_0001684 estimated overall survival in pediatric AML patients.
CONCLUSION
CircRNA profile is intensively implicated in the disease risk and treatment response of pediatric AML, especially that circ_0032891, circ_0000544, circ_0076995, and circ_0001684 are related to pediatric AML risk, CR achievement, and survival.
目的
环状 RNA（circRNA）是一种新型的非编码 RNA，与白血病的发生和治疗反应密切相关。本研究旨在筛选和验证可评估儿科急性髓系白血病（AML）疾病风险和诱导治疗反应的候选环状 RNA（circRNA）。
方法
通过微阵列分析，从 4 例完全缓解（CR）儿科 AML 患者、4 例非 CR 儿科 AML 患者和 4 例对照者的骨髓样本中筛选差异表达的环状 RNA（DECs）。通过逆转录定量聚合酶链反应（RT-qPCR）在 40 例儿科 AML 患者和 10 例对照者中选择并验证 10 个候选环状 RNA。
结果
微阵列检测发现，与对照组相比，AML 患儿中有 378 个上调的 DECs 和 688 个下调的 DECs，CR AML 患儿中有 832 个上调的 DECs和 950 个下调的 DECs。然后，交叉分析确定了 441 个与儿科 AML 风险和 CR 相关的 DECs。在更大样本量的人群中进一步验证 10 个候选环状 RNA 显示，circ_0032891、circ_0076995、circ_0014352、circ_0047663、circ_0007444、circ_0001684、circ_0000544 和 circ_0005354 与儿科 AML 风险相关；circ_0032891、circ_0076995、circ_0014352、circ_0047663、circ_0007444、circ_0001684 和 circ_0000544 与儿科 AML 患者的 CR 相关。关于候选环状 RNA 与生存状况的相关性，只有 circ_0032891、circ_0076995 和 circ_0000544 预测无事件生存；circ_0076995 和 circ_0001684 估计儿科 AML 患者的总生存。
结论
环状 RNA 谱与儿科 AML 的疾病风险和治疗反应密切相关，尤其是 circ_0032891、circ_0000544、circ_0076995 和 circ_0001684 与儿科 AML 风险、CR 相关和生存相关。
Zotero 插件