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循环外泌体miR-17-92簇作为胃癌患者一种新型的非侵入性诊断标志物。

Circulating exosomal miR-17-92 cluster serves as a novel noninvasive diagnostic marker for patients with gastric cancer.

作者信息

Han Ye, Guo Xing-Po, Zhi Qiao-Ming, Xu Jing-Jing, Liu Fei, Kuang Yu-Ting

机构信息

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.

Department of Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.

出版信息

World J Gastrointest Oncol. 2025 May 15;17(5):104776. doi: 10.4251/wjgo.v17.i5.104776.

DOI:10.4251/wjgo.v17.i5.104776
PMID:40487936
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12142227/
Abstract

BACKGROUND

Gastric cancer (GC) is among the most common malignant tumors and remains a leading cause of cancer-related mortality worldwide. Furthermore, exosomal miRNAs are regarded as promising noninvasive biomarkers for diagnosing malignant tumors.

AIM

To investigate the expression of exosomal miR-17-92 clusters and develop a potential biomarker for GC diagnosis.

METHODS

Exosomes were isolated from serum samples obtained from 72 GC patients and 20 healthy controls. The isolated exosomes were validated using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Exosomal RNA was then extracted, and the expression profile of the miR-17-92 cluster was analyzed using qRT-PCR. Statistical methods were employed to evaluate the relationship between the serum exosomal miR-17-92 cluster expression and the clinicopathological parameters of GC patients as well as to assess the diagnostic utility of these miRNAs.

RESULTS

The expression of four members of the exosomal miR-17-92 cluster-miR-17, miR-18, miR-19a, and miR-92-was significantly upregulated in the serum samples of patients with GC compared with those of healthy controls. The miR-17-92 cluster panel demonstrated substantially higher clinical diagnostic value for GC than any individual component or pair. Additionally, the expression of traditional tumor biomarkers-carcinoembryonic antigen and carbohydrate antigen 19-9-was significantly elevated in the serum of patients with GC compared with that of healthy controls. Each biomarker, whether alone or in combination, effectively differentiated the patients from healthy controls. Furthermore, a combined panel of the two traditional tumor biomarkers and the four miR-17-92 cluster members exhibited the highest diagnostic accuracy for GC. Elevated miR-17-92 expression was also strongly associated with tumor size, tumor depth, lymph node metastasis, distant metastasis, and tumor-node-metastasis stage.

CONCLUSION

Our findings revealed that the circulating exosomal miR-17-92 cluster may be used as a potential noninvasive biomarker to improve diagnostic efficiency for GC.

摘要

背景

胃癌(GC)是最常见的恶性肿瘤之一,仍然是全球癌症相关死亡的主要原因。此外,外泌体微小RNA(miRNA)被认为是诊断恶性肿瘤的有前景的非侵入性生物标志物。

目的

研究外泌体miR-17-92簇的表达,并开发一种用于胃癌诊断的潜在生物标志物。

方法

从72例胃癌患者和20例健康对照者的血清样本中分离外泌体。使用透射电子显微镜、纳米颗粒跟踪分析和蛋白质印迹法对分离的外泌体进行验证。然后提取外泌体RNA,并使用定量逆转录聚合酶链反应(qRT-PCR)分析miR-17-92簇的表达谱。采用统计学方法评估血清外泌体miR-17-92簇表达与胃癌患者临床病理参数之间的关系,并评估这些miRNA的诊断效用。

结果

与健康对照者相比,胃癌患者血清样本中外泌体miR-17-92簇的四个成员——miR-17、miR-18、miR-19a和miR-92的表达显著上调。miR-17-92簇组合对胃癌的临床诊断价值远高于任何单个成分或组合。此外,与健康对照者相比,胃癌患者血清中传统肿瘤生物标志物——癌胚抗原和糖类抗原19-9的表达显著升高。每种生物标志物,无论单独使用还是联合使用,都能有效地区分患者和健康对照者。此外,两种传统肿瘤生物标志物和四个miR-17-92簇成员的组合对胃癌的诊断准确性最高。miR-17-92表达升高也与肿瘤大小、肿瘤深度、淋巴结转移、远处转移和肿瘤-淋巴结-转移分期密切相关。

结论

我们的研究结果表明,循环外泌体miR-17-92簇可作为一种潜在的非侵入性生物标志物,以提高胃癌的诊断效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/c222b6db6fef/104776-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/b1071a1e0216/104776-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/d5140e62c6fe/104776-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/bf936b7d8231/104776-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/c222b6db6fef/104776-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/b1071a1e0216/104776-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/d5140e62c6fe/104776-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/bf936b7d8231/104776-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/762e/12142227/c222b6db6fef/104776-g004.jpg

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