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miR-21-5p、miR-30c-5p和miR-182-5p作为透明细胞肾细胞癌生物标志物的研究:罗马尼亚东南部队列研究

The miR-21-5p, miR-30c-5p, and miR-182-5p as Biomarkers in Clear Cell Renal Cell Carcinoma: A Southeastern Romanian Cohort Study.

作者信息

Burlacu Ionuț, Așchie Mariana, Cozaru Georgeta Camelia, Deacu Mariana, Vizireanu Gabriela Miruna, Mitroi Adrian Nelutu, Mitroi Anca Florentina, Brînzan Costel Stelian

机构信息

Pathology Department, Sf. Apostol Andrei Clinical Emergency County Hospital, 145 Tomis Blvd, 900591 Constanta, Romania.

CEDMOG Center, Ovidius University, 145 Tomis Blvd., 900527 Constanta, Romania.

出版信息

Genes (Basel). 2025 May 28;16(6):650. doi: 10.3390/genes16060650.

Abstract

BACKGROUND

This study aimed to evaluate the expression and clinical relevance of three mature miRNAs (miR-21-5p, miR-30c-5p, and miR-182-5p) in patients with clear cell renal cell carcinoma (ccRCC) from southeast Romania, and to explore their potential as non-invasive diagnostic and prognostic biomarkers.

METHODS

miRNA expression levels were measured using TaqMan MGB and qRT-PCR in paired tumor and adjacent non-cancerous tissues, as well as in serum-derived exosomes, from 26 ccRCC patients. Statistical analysis included the Wilcoxon test for group comparisons and non-parametric tests for correlations with clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance, and miRNA panels were constructed for improved accuracy.

RESULTS

Significant dysregulation of the investigated miRNAs was observed. miR-21-5p was markedly overexpressed in both tumor tissues (3.46-fold, < 0.001) and serum exosomes (3.26-fold, < 0.001). miR-182-5p showed modest overexpression in tissues (0.56-fold, < 0.001) and serum (0.85-fold, < 0.001), whereas miR-30c-5p was significantly downregulated in both tissues (2.48-fold decrease, < 0.001) and serum exosomes (2.29-fold decrease, = 0.0003). Elevated miR-182-5p expression correlated with tumor localization in the right kidney ( = 0.02) and lymph node involvement ( = 0.04). Similarly, higher miR-21-5p levels in serum exosomes were associated with right-sided tumors ( = 0.01). ROC analysis revealed distinct expression profiles for all three miRNAs between ccRCC and normal tissue, both in tissue and exosomal samples (all < 0.05). Combined biomarker panels yielded high diagnostic performance (AUC = 0.94 for tissue, AUC = 0.93 for exosomes).

CONCLUSIONS

This study underscores the potential of miR-21-5p, miR-30c-5p, and miR-182-5p as non-invasive biomarkers for ccRCC diagnosis and prognosis. The use of serum exosomal miRNA panels offers a promising alternative to tissue-based diagnostics in Romanian ccRCC patients.

摘要

背景

本研究旨在评估罗马尼亚东南部透明细胞肾细胞癌(ccRCC)患者中三种成熟微小RNA(miR-21-5p、miR-30c-5p和miR-182-5p)的表达及其临床相关性,并探索它们作为非侵入性诊断和预后生物标志物的潜力。

方法

采用TaqMan MGB和qRT-PCR检测了26例ccRCC患者的配对肿瘤组织和癌旁非肿瘤组织以及血清来源外泌体中的微小RNA表达水平。统计分析包括用于组间比较的Wilcoxon检验以及用于与临床病理特征相关性分析的非参数检验。采用受试者工作特征(ROC)曲线评估诊断性能,并构建微小RNA组合以提高准确性。

结果

观察到所研究的微小RNA存在明显的失调。miR-21-5p在肿瘤组织(3.46倍,<0.001)和血清外泌体(3.26倍,<0.001)中均显著上调。miR-182-5p在组织(0.56倍,<0.001)和血清(0.85倍,<0.001)中表现为适度上调,而miR-30c-5p在组织(降低2.48倍,<0.001)和血清外泌体(降低2.29倍,=0.0003)中均显著下调。miR-182-5p表达升高与肿瘤位于右肾(=0.02)和淋巴结受累(=0.04)相关。同样,血清外泌体中较高的miR-21-5p水平与右侧肿瘤相关(=0.01)。ROC分析显示,在ccRCC和正常组织之间,无论是在组织样本还是外泌体样本中,所有三种微小RNA均具有明显不同的表达谱(均<0.05)。联合生物标志物组合具有较高的诊断性能(组织样本的AUC = 0.94,外泌体样本的AUC = 0.93)。

结论

本研究强调了miR-21-5p、miR-30c-5p和miR-182-5p作为ccRCC诊断和预后非侵入性生物标志物的潜力。对于罗马尼亚ccRCC患者,使用血清外泌体微小RNA组合为基于组织的诊断提供了一种有前景的替代方法。

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