| 杨海华,周苏娜,王学全.非小细胞肺癌自适应放疗患者血浆外泌体微小RNA差异表达谱和生物信息学分析[J].肿瘤学杂志,2021,27(9):728-734. |
| 非小细胞肺癌自适应放疗患者血浆外泌体微小RNA差异表达谱和生物信息学分析 |
| Differential Expression of Plasma Exosomal MicroRNA in Non-small Cell Lung Cancer Patients with Adaptive Radiotherapy and Its Bioinformatic Analysis |
| 投稿时间：2021-08-08 |
| DOI：10.11735/j.issn.1671-170X.2021.09.B006 |
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| 中文关键词: 非小细胞肺癌 自适应放疗 血浆 外泌体miRNA 生物信息学分析 |
| 英文关键词:non-small cell lung cancer adaptive radiotherapy plasma exosomal miRNA bioinformatic analysis |
| 基金项目:浙江省基础公益研究计划（LGF21H160027）；浙江省医药卫生科技计划项目（2020PY001，2021PY038） |
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| 中文摘要: |
| 摘 要：［目的］ 分析Ⅲ期非小细胞肺癌(non-small cell lung cancer，NSCLC)自适应放疗中不同放射敏感性患者的血浆外泌体微小RNA (microRNA，miRNA)差异表达谱，并应用生物信息学分析外泌体miRNA的作用。［方法］ NSCLC患者接受自适应放疗20次时的胸部增强CT进行肿瘤评估，划分为放射敏感组与放射抵抗组，从中筛选出5对进行下一步研究。 通过QIAseq建库方法构建稳定的 miRNA 特异文库，并利用Illumina高通量测序技术检测miRNA差异表达谱。对差异miRNA靶基因进行生物信息学分析，分析其涉及的主要生物学功能及信号通路。［结果］ 与放射敏感患者相比，放射抵抗患者血浆外泌体中共有 142个miRNA异常表达，其中下调 42个，上调 100 个。通过基因本体富集及京都基因与基因组百科全书的通路富集分析，上述差异表达miRNA的靶基因功能主要富集于TGF-β、Hedgehog、mTOR、p53等信号通路，涉及RNA聚合酶、泛素样蛋白转移酶等多种细胞生化代谢途径，并参与细胞黏附、细胞周期、衰老等多种生物学过程。 ［结论］ 不同放射敏感性NSCLC患者血浆外泌体miRNA表达谱发生了明显变化，可能通过TGF-β等信号通路在NSCLC放射敏感性调控中发挥重要作用。 |
| 英文摘要: |
| Abstract：［Objective］ To analyze differential microRNA(miRNA) expression profile in plasma exosomes of stage Ⅲ non-small cell lung cancer(NSCLC) patients with different radiosensitivity who received adaptive radiotherapy(ART)， and bioinformatics analysis was applied to explore the role of miRNA. ［Methods］ The tumor regression was evaluated by enhanced chest CT at 20 fractions in stage Ⅲ NSCLC patients who received ART. Patients were divided into radiation sensitive group and radiation resistance groups， and 5 pairs samples were selected for further research. A stable miRNA specific library was constructed by QIAseq library construction method. The differential miRNA expression profile was detected by Illumina high-throughput sequencing. Bioinformatic analysis was utilized to investigate the involved main biological functions and signal pathways of the differential miRNA-targeted-genes. ［Results］ Compared with radiation sensitive group， there were 142 significantly differentially expressed miRNAs in plasma exosomes of the radiation resistance group. Among them， 42 miRNAs were downregulated and 100 miRNAs were upregulated. By gene ontology(GO) enrichment and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis， the targeted genes of differential expressed miRNA were mainly enriched in TGF-β， Hedgehog， mTOR， p53 and other signaling pathway. Moreover， they participated in varies of cellular biochemical metabolic pathways including RNA polymerase， ubiquitin-like protein transferase， and so on， and different biological processes such as adhesion， cell cycle and senescence． ［Conclusion］ The remarkably differential miRNA expression profile is detected in plasma exosomes of NSCLC patients with different radiosensitivity， and might play a critical function in the radiosensitivity regulation of NSCLC through TGF-β signaling pathway and so on. |
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