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鼻咽癌放化疗完全缓解患者的循环微小RNA表达谱

Circulation microRNA expression profiles in patients with complete responses to chemoradiotherapy in nasopharyngeal carcinoma.

作者信息

Wardana Tirta, Chasanah Siti Nur, Oktriani Risky, Herawati Cita, Anwar Sumadi Lukman, Astuti Indwiani, Mubarika Haryana Sofia

机构信息

Department of Biomedicine, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia.

Graduate Student, Biomedical Science, Faculty of Medicine, Nursing, and Public Health, Gadjah Mada University, Yogyakarta, Indonesia.

出版信息

Noncoding RNA Res. 2022 Sep 11;7(4):233-241. doi: 10.1016/j.ncrna.2022.09.005. eCollection 2022 Dec.

DOI:10.1016/j.ncrna.2022.09.005
PMID:36203524
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9519485/
Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) is endemic cancer in Southeast Asia with a relatively poor prognosis. Chemoradiotherapy is a primary treatment that advantages certain patients, particularly in the early stages. New predictive and prognostic biomarkers are required to guide and select the best treatment.

AIMS

To evaluate the circulation expression profile of microRNAs (miRNAs) associated with responses to chemoradiotherapy in nasopharyngeal carcinoma.

METHODS

Peripheral blood from 17 patients was collected before and after chemotherapy and radiotherapy. Differential expression circulating miRNAs were analyzed using microRNA Cancer Panels and were compared among patients with complete responses. Differential expression analysis using GenEx 7 Multid, statistic represented by GraphPad Prism 9. Alterations mechanism signaling pathways and biological function using IPA (Ingenuity Pathways Analysis).

RESULTS

Using microRNAs Cancer Plate consisting of 116 miRNAs, we identified ten circulating miRNAs that were differentially expressed in NPC patients after chemoradiotherapy. Unsupervised clustering and confirmation using qRT-PCR showed that miR-483-5p, miR-584-5p, miR-122-5p, miR-7-5p, miR-150-5p were overexpressed and miRNA are miR-421, miR-133a-3p, miR-18a-5p, miR-106b-3p, miR-339-5p were significantly downregulated after chemoradiotherapy (p < 0.0001). In addition, ROC analysis through AUC (Area Under Curve) with 99% confidence interval (CI) p value < 0.0001. Gene enrichment analysis of microRNAs and the targeted proteins revealed that the main involved pathways for chemoradiotherapy in NPC were cell death and survival signaling pathways.

CONCLUSION

qPCR profiling in circulating blood compared before and after chemoradiotherapy in nasopharyngeal carcinoma can identify pathways involved in treatment responses. miR-483-5p, miR-584-5p, miR-122-5p, miR-7-5p, miR-150-5p, miR-421, miR-133a-3p, miR-18a-5p, miR-106b-3p, miR-339-5p are differentially regulated after chemoradiotherapy in NPC.

摘要

背景

鼻咽癌(NPC)是东南亚地区的地方性癌症,预后相对较差。放化疗是主要治疗方法,对某些患者有益,尤其是早期患者。需要新的预测和预后生物标志物来指导和选择最佳治疗方案。

目的

评估与鼻咽癌放化疗反应相关的微小RNA(miRNA)的循环表达谱。

方法

收集17例患者放化疗前后的外周血。使用微小RNA癌症检测板分析循环miRNA的差异表达,并在完全缓解的患者中进行比较。使用GenEx 7 Multid进行差异表达分析,由GraphPad Prism 9统计。使用IPA(Ingenuity通路分析)分析改变机制的信号通路和生物学功能。

结果

使用由116种miRNA组成的微小RNA癌症检测板,我们鉴定出10种在鼻咽癌患者放化疗后差异表达的循环miRNA。无监督聚类和qRT-PCR验证显示,放化疗后miR-483-5p、miR-584-5p、miR-122-5p、miR-7-5p、miR-150-5p上调,miR-421、miR-133a-3p、miR-18a-5p、miR-106b-3p、miR-339-5p显著下调(p < 0.0001)。此外,通过AUC(曲线下面积)进行的ROC分析,99%置信区间(CI)p值 < 0.0001。对miRNA及其靶向蛋白的基因富集分析表明,鼻咽癌放化疗主要涉及的通路是细胞死亡和生存信号通路。

结论

鼻咽癌放化疗前后循环血液中的qPCR分析可以识别参与治疗反应的通路。miR-483-5p、miR-584-5p、miR-122-5p、miR-7-5p、miR-150-5p、miR-421、miR-133a-3p、miR-18a-5p、miR-106b-3p、miR-339-5p在鼻咽癌放化疗后受到差异调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac6/9519485/f87f54ad884f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac6/9519485/e09eac98b886/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac6/9519485/ad5996877c81/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac6/9519485/f87f54ad884f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac6/9519485/e09eac98b886/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac6/9519485/ad5996877c81/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ac6/9519485/f87f54ad884f/gr3.jpg

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