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初步研究使用小型血浆细胞外囊泡 miRNA 面板作为喉癌早期诊断和预后的潜在生物标志物。

Preliminary study using a small plasma extracellular vesicle miRNA panel as a potential biomarker for early diagnosis and prognosis in laryngeal cancer.

机构信息

Department of Otolaryngology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, 200031, Shanghai, China.

出版信息

Cell Oncol (Dordr). 2023 Aug;46(4):1015-1030. doi: 10.1007/s13402-023-00792-y. Epub 2023 Mar 25.

Abstract

PURPOSE

Plasma extracellular vesicle (EV) miRNAs are important biomarkers for body fluid biopsy. The purpose of this study was to screen and construct a plasma small EV (sEV) miRNA panel as a biomarker for diagnosis and prognosis in laryngeal squamous cell carcinoma (LSCC).

METHODS

Plasma sEV miRNAs from 6 LSCC patients with three typical anatomical sites and 3 normal controls (NCs) were analyzed by next-generation sequencing. The aberrant expression profile of sEV miRNAs was compared with the online databases of LSCC to construct and verify the diagnostic and prognostic panel by machine learning. Additionally, quantitative real-time polymerase chain reaction (qRT‒PCR) was performed to validate the diagnostic efficacy of the screened miRNAs in an independent clinical cohort.

RESULTS

A plasma sEV miRNA panel (consisting of hsa-miR-139-3p, hsa-miR-486-5p, hsa-miR-944, hsa-miR-320b and hsa-miR-455-5p) was successfully constructed for the early diagnosis and prognosis of LSCC and showed good predictive potential with AUCs of 0.782, 1.000, 0.716, and 0.875 by an artificial neural network (ANN) panel in independent datasets. This panel was further validated in an independent cohort consisting of 84 clinical cases (48 LSCC and 36 NCs). In the validation cohort, the AUC of the 5 individual miRNAs ranged from 0.721 to 0.837. The accuracy was further increased by the logistic model, which further increased the AUC to 0.959 by adjusting for the number of miRNAs. The miRNA‒mRNA regulatory network and immune function analysis revealed the possible underlying pathogenesis of LSCC.

CONCLUSION

Plasma sEV miRNA panels can be promising plasma biomarkers for predicting early diagnosis and prognosis in LSCC.

摘要

目的

血浆细胞外囊泡(EV)miRNA 是体液活检的重要生物标志物。本研究旨在筛选并构建血浆小 EV(sEV)miRNA 谱作为喉鳞状细胞癌(LSCC)诊断和预后的生物标志物。

方法

通过下一代测序分析 6 例具有 3 个典型解剖部位的 LSCC 患者和 3 例正常对照(NC)的血浆 sEV miRNA。将 sEV miRNA 的异常表达谱与 LSCC 的在线数据库进行比较,通过机器学习构建和验证诊断和预后谱。此外,通过定量实时聚合酶链反应(qRT-PCR)在独立临床队列中验证筛选 miRNA 的诊断效果。

结果

成功构建了用于 LSCC 早期诊断和预后的血浆 sEV miRNA 谱(由 hsa-miR-139-3p、hsa-miR-486-5p、hsa-miR-944、hsa-miR-320b 和 hsa-miR-455-5p 组成),并通过人工神经网络(ANN)在独立数据集显示出良好的预测潜力,AUC 为 0.782、1.000、0.716 和 0.875。该谱在由 84 例临床病例(48 例 LSCC 和 36 例 NC)组成的独立队列中进一步验证。在验证队列中,5 个单独 miRNA 的 AUC 范围为 0.721 至 0.837。通过逻辑模型进一步提高准确性,通过调整 miRNA 的数量进一步将 AUC 提高至 0.959。miRNA-mRNA 调控网络和免疫功能分析揭示了 LSCC 可能的潜在发病机制。

结论

血浆 sEV miRNA 谱可作为预测 LSCC 早期诊断和预后的有前途的血浆生物标志物。

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