Diagnostic Potential of Exosomal and Non-Exosomal Biomarkers in Lung Cancer: A Comparative Analysis Using a Rat Model of Lung Carcinogenesis.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2025-06-16 DOI:10.3390/ncrna11030047

Sherien M El-Daly, Sahar S Abdelrahman, Amira Mohamed Abd El-Jawad, Mahmoud A Abdel-Monem, Gamila S M El-Saeed

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引用次数: 0

Abstract

Background: Identifying liquid biopsy biomarkers with high efficacy is crucial for cancer diagnosis. Exosomal cargo, including miRNAs and proteins, offers enhanced stability in biofluids compared with their free circulating forms, but direct comparisons of their diagnostic performance remain limited. This study evaluates and compares the diagnostic value of selected miRNAs and protein markers in exosomal versus non-exosomal fractions across stages of lung carcinogenesis in a rat model.

Methods: Lung cancer was induced in rats, and blood and lung tissue samples were collected at consecutive stages of tumor induction. We investigated the expression patterns of key miRNAs (miR-19b, miR-21, and miR-145) in exosomes, serum, and tissue and quantified levels of tumor biomarkers CEA and CYFRA 21-1 in exosomal and serum fractions.

Results: Our results revealed distinct expression patterns of the evaluated miRNAs across exosomes, serum, and tissue, throughout different stages of tumor induction. The expression of exosomal miRNAs dynamically changed in parallel with the tumor induction process, demonstrating high diagnostic efficacy. Specifically, exosomal miR-19b and miR-21 were significantly upregulated from an early induction stage, whereas their serum and tissue forms increased only during the late stages of induction. On the other hand, miR-145 was consistently downregulated across all fractions at every stage. Both exosomal and serum CEA levels increased significantly during tumor induction, while serum CYFRA 21-1 outperformed its exosomal counterpart. Strong positive correlations linked exosomal miR-19b and miR-145 with their non-exosomal counterparts, while moderate correlations were seen for miR-21 and the protein markers.

Conclusions: Our findings underscore the value of integrating exosomal biomarkers in liquid biopsies, highlighting their potential to improve early detection and monitoring of lung cancer development.

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外泌体和非外泌体生物标志物在肺癌中的诊断潜力：使用大鼠肺癌发生模型的比较分析。

背景：鉴别高效的液体活检生物标志物对癌症诊断至关重要。外泌体货物，包括mirna和蛋白质，与其自由循环形式相比，在生物体液中提供了更高的稳定性，但对其诊断性能的直接比较仍然有限。本研究在大鼠模型中评估和比较了外泌体与非外泌体部分中选择的mirna和蛋白质标志物在肺癌发生阶段的诊断价值。方法：大鼠诱导肺癌，在肿瘤诱导的连续阶段采集血液和肺组织标本。我们研究了外泌体、血清和组织中关键mirna （miR-19b、miR-21和miR-145）的表达模式，并量化了外泌体和血清中肿瘤生物标志物CEA和CYFRA 21-1的水平。结果：我们的研究结果揭示了在肿瘤诱导的不同阶段，所评估的mirna在外泌体、血清和组织中的不同表达模式。外泌体mirna的表达与肿瘤诱导过程平行动态变化，具有较高的诊断效能。具体而言，外泌体miR-19b和miR-21在诱导早期显著上调，而其血清和组织形式仅在诱导后期增加。另一方面，miR-145在每个阶段的所有分数中都持续下调。在肿瘤诱导过程中，外泌体和血清CEA水平均显著升高，而血清CYFRA 21-1表现优于其外泌体对应体。外泌体miR-19b和miR-145与其非外泌体对应物之间存在强正相关，而miR-21与蛋白质标记物之间存在中度相关性。结论：我们的研究结果强调了在液体活检中整合外泌体生物标志物的价值，强调了它们在改善肺癌发展的早期发现和监测方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.