Identification and validation of circulating exosome-derived microRNAs for the early diagnosis of gastric cancer

Li Yan; Yang Liu; Zhang Yong; Liu Yongyu; Li Zongxin; Han Hongyan; Deng Kun

doi:10.13406/j.cnki.cyxb.003782

您当前的位置：

首页 >

文章列表页 >

Identification and validation of circulating exosome-derived microRNAs for the early diagnosis of gastric cancer

Precision medicine in cancer and translational studies | 更新时间：2025-10-21

- Identification and validation of circulating exosome-derived microRNAs for the early diagnosis of gastric cancer
- Journal of Chongqing Medical University Vol. 50, Issue 9, Pages: 1236-1241(2025)
- 作者机构：
  
  1.重庆医科大学附属第三医院检验科，重庆 401120
  2.重庆大学生物工程学院生物流变科学与技术教育部重点实验室，重庆 400044
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003782
  CLC： R735.2
- Received：03 November 2023，
  
  Revised：2024-03-16，
  
  Accepted：19 March 2024，
  
  Published：28 September 2025
- 稿件说明：
移动端阅览
李燕,杨柳,张勇,等.循环外泌体源性微RNA用于胃癌早期诊断的筛选和鉴定[J].重庆医科大学学报,2025,50(9):1236-1241.

Li Yan,Yang Liu,Zhang Yong,et al.Identification and validation of circulating exosome-derived microRNAs for the early diagnosis of gastric cancer[J].Journal of Chongqing Medical University,2025,50(9):1236-1241.
李燕,杨柳,张勇,等.循环外泌体源性微RNA用于胃癌早期诊断的筛选和鉴定[J].重庆医科大学学报,2025,50(9):1236-1241. DOI： 10.13406/j.cnki.cyxb.003782.

Li Yan,Yang Liu,Zhang Yong,et al.Identification and validation of circulating exosome-derived microRNAs for the early diagnosis of gastric cancer[J].Journal of Chongqing Medical University,2025,50(9):1236-1241. DOI： 10.13406/j.cnki.cyxb.003782.

摘要

目的

通过筛查外周血中肿瘤特异性来源的外泌体中的微RNA，建立一种新的胃癌早期诊断方法。

方法

从基因表达综合数据库中下载胃癌外泌体数据集GSE148334和GSE130654，以logFC

1或logFC

-1，

0.05为标准筛选差异RNAs；通过TargetScan和ENCORI数据库预测mRNA-miRNA-lncRNA之间的调控关系，用Cytoscape软件绘制ceRNA网络并筛选Hub基因进行验证。纳入27例早期胃癌患者、25例健康对照和25例其他癌症患者为研究对象，通过超速离心法分离血清外泌体。提取血清和外泌体样本中的RNA进行实时荧光定量聚合酶链式反应（real-time quantitative polymerase chain reaction，RT-qPCR）试验，分析Hub基因在各组的表达情况。

结果

通过生物信息学方法筛选出3个Hub基因

hsa-miR-105-5p、hsa-miR-219b-3p

和

hsa-miR-889-3p

，RT-qPCR结果显示

hsa-miR-219b-3p

在胃癌组血清和外泌体样本中的表达均明显高于健康对照组和其他癌组（血清：4.050±2.697，1.357±0.857，1.934±2.434；外泌体：2.525±1.518，0.774±0.559，1.259±2.127），差异有统计学意义（

0.05），而

hsa-miR-105-5p

和

hsa-miR-889-3p

在胃癌组和其他两组之间表达差异无统计学意义（

0.05）。外泌体hsa-miR-219b-3p的受试者工作特征曲线下面积为0.896（95%CI=0.800~0.993），明显优于传统肿瘤标志物癌胚抗原（

=0.015）、糖类抗原19-9（

=0.021）和糖类抗原72-4（

=0.005），所以外泌体hsa-miR-219b-3p在胃癌患者中具有更优的诊断效能。

结论

血清外泌体来源的hsa-miR-219b-3p有作为早期胃癌诊断标志物的潜力。

Abstract

Objective

To establish a novel method for the early diagnosis of gastric cancer（GC） by screening for the microRNAs within tumor-specific exosomes in peripheral blood.

Methods

The gene expression omnibus database was used to download the GSE148334 and GSE130654 datasets of GC exosomes，and differentially expressed RNAs were obtained according to logFC

1 or logFC

-1 and

0.05. TargetScan and ENCORI databases

were used to predict the regulatory relationship between mRNA，miRNA，and lncRNA，and Cytoscape software was used to construct a ceRNA network and identify hub genes for validation. A total of 27 patients with early-stage GC，25 healthy controls，and 25 patients with other types of cancer were enrolled，and the ultracentrifugation method was used to isolate exosomes in serum. RT-qPCR was performed for RNA in serum and exosome samples to analyze the expression of hub genes in each group.

Results

Three hub genes were identified by the bioinformatics method，namely

hsa-miR-105-5p

，

hsa-miR-219b-3p

，and

hsa-miR-889-3p

，and RT-qPCR showed that the GC group had a significantly higher expression level of

hsa-miR-219b-3p

in serum and exosome samples than the healthy control group and the other cancer group（serum：4.050±2.697 vs. 1.357±0.857/1.934±2.434，

0.05；exosomes：2.525±1.518 vs. 0.774±0.559/1.259±2.127，

0.05），while there were no significant differences in the expression levels of

hsa-miR-889-3p

and

hsa-miR-105-5p

between the GC group and the other two groups（

0.05）. The receiver operating characteristic（ROC） curve showed that hsa-miR-219b-3p in serum-derived exosomes had an area under the ROC curve of 0.896（95%CI=0.800-0.993），which was significantly better than the traditional tumor markers of carcinoembryonic antigen （

=0.015），CA19-9（

=0.021），and CA72-4（

=0.005），and therefore，exosomal hsa-miR-219b-3p showed a better diagnostic efficacy in GC patients.

Conclusion

This study shows that hsa-miR-219b-3p in serum-derived exosomes can be used as a potential marker for the early diagnosis of GC in clinical practice.

关键词

Keywords

references

Sung H ， Ferlay J ， Siegel RL ， et al . Global cancer statistics 2020： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin ， 2021 ， 71 （ 3 ）： 209 - 249 .

Joshi SS ， Badgwell BD . Current treatment and recent progress in gastric cancer [J ] . CA Cancer J Clin ， 2021 ， 71 （ 3 ）： 264 - 279 .

Bouriez D ， Giraud J ， Gronnier C ， et al . Efficiency of all-trans retinoic acid on gastric cancer： a narrative literature review [J ] . Int J Mol Sci ， 2018 ， 19 （ 11 ）： 3388 .

Guo X ， Peng YH ， Song QY ， et al . A liquid biopsy signature for the early detection of gastric cancer in patients [J ] . Gastroenterology ， 2023 ， 165 （ 2 ）： 402 - 413 .

Pietrykowska H ， Sierocka I ， Zielezinski A ， et al . Biogenesis，conservation，and function of miRNA in liverworts [J ] . J Exp Bot ， 2022 ， 73 （ 13 ）： 4528 - 4545 .

Rupaimoole R ， Slack FJ . MicroRNA therapeutics： towards a new era for the management of cancer and other diseases [J ] . Nat Rev Drug Discov ， 2017 ， 16 （ 3 ）： 203 - 222 .

Shen JZ ， Liang CH ， Su XM ， et al . Dysfunction and CeRNA network of the tumor suppressor miR-637 in cancer development and prognosis [J ] . Biomark Res ， 2022 ， 10 （ 1 ）： 72 .

Qi X ， Lin YX ， Chen JJ ， et al . Decoding competing endogenous RNA networks for cancer biomarker discovery [J ] . Brief Bioinform ， 2020 ， 21 （ 2 ）： 441 - 457 .

Akhbari MH ， Zafari Z ， Sheykhhasan M . Competing endogenous RNAs （ceRNAs） in colorectal cancer： a review [J ] . Expert Rev Mol Med ， 2022 ， 24 ： e27 .

Zhao ML ， Feng JG ， Tang LL . Competing endogenous RNAs in lung cancer [J ] . Cancer Biol Med ， 2021 ， 18 （ 1 ）： 1 - 20 .

Xu JC ， Xu J ， Liu XY ， et al . The role of lncRNA-mediated CeRNA regulatory networks in pancreatic cancer [J ] . Cell Death Discov ， 2022 ， 8 （ 1 ）： 287 .

Fan QW ， Liu BR . Comprehensive analysis of a long noncoding RNA-associated competing endogenous RNA network in colorectal cancer [J ] . Onco Targets Ther ， 2018 ， 11 ： 2453 - 2466 .

Hussen BM ， Hidayat HJ ， Salihi A ， et al . MicroRNA： A signature for cancer progression [J ] . Biomed Pharmacother ， 2021 ， 138 ： 111528 .

Paterson E ， Blenkiron C ， Danielson K ， et al . Recommendations for extracellular vesicle miRNA biomarker research in the endometrial cancer context [J ] . Transl Oncol ， 2022 ， 23 ： 101478 .

Kalluri R ， LeBleu VS . The biology ， function ， and biomedical applications of exosomes [J ] . Science ， 2020 ， 367 （ 6478 ）： eaau6977 .

Preethi KA ， Selvakumar SC ， Ross K ， et al . Liquid biopsy：Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer [J ] . Mol Cancer ， 2022 ， 21 （ 1 ）： 54 .

Yoshimura A ， Sawada K ， Nakamura K ， et al . Exosomal miR-99a-5p is elevated in sera of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in neighboring peritoneal mesothelial cells [J ] . BMC Cancer ， 2018 ， 18 （ 1 ）： 1065 .

Shen SJ ， Song Y ， Zhao B ， et al . Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis [J ] . Cell Commun Signal ， 2021 ， 19 （ 1 ）： 20 .

Li ZG ， Chen JH ， Zhao SB ， et al . Discovery and validation of novel biomarkers for detection of cervical cancer [J ] . Cancer Med ， 2021 ， 10 （ 6 ）： 2063 - 2074 .

Qian XQ ， Xie F ， Wei HB ， et al . Identification of key circulating exosomal microRNAs in gastric cancer [J ] . Front Oncol ， 2021 ， 11 ： 693360 .

Lu X ， Lu JX ， Wang SQ ， et al . Circulating serum exosomal miR-92a-3p as a novel biomarker for early diagnosis of gastric cancer [J ] . Future Oncol ， 2021 ， 17 （ 8 ）： 907 - 919 .

Shi YT ， Wang ZH ， Zhu XJ ， et al . Exosomal miR-1246 in serum as a potential biomarker for early diagnosis of gastric cancer [J ] . Int J Clin Oncol ， 2020 ， 25 （ 1 ）： 89 - 99 .

Domenyuk V ， Zhong ZY ， Stark A ， et al . Plasma exosome profiling of cancer patients by a next generation systems biology approach [J ] . Sci Rep ， 2017 ， 7 ： 42741 .

Wang M ， Ji S ， Shao G ， et al . Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients [J ] . Clin Transl Oncol ， 2018 ， 20 （ 7 ）： 906 - 911 .

Machlowska J ， Maciejewski R ， Sitarz R . The pattern of signatures in gastric cancer prognosis [J ] . Int J Mol Sci ， 2018 ， 19 （ 6 ）： 1658 .

Necula L ， Matei L ， Dragu D ， et al . Recent advances in gastric cancer early diagnosis [J ] . World J Gastroenterol ， 2019 ， 25 （ 17 ）： 2029 - 2044 .

Wang HP ， Jin WB ， Wan CQ ， et al . Diagnostic value of combined detection of CA72-4，CA19-9，and carcinoembryonic antigen comparing to CA72-4 alone in gastric cancer： a systematic review and meta-analysis [J ] . Transl Cancer Res ， 2022 ， 11 （ 4 ）： 848 - 856 .

He BX ， Zhao ZY ， Cai QD ， et al . miRNA-based biomarkers，therapies，and resistance in Cancer [J ] . Int J Biol Sci ， 2020 ， 16 （ 14 ）： 2628 - 2647 .

Sun ZQ ， Shi K ， Yang SX ， et al . Effect of exosomal miRNA on cancer biology and clinical applications [J ] . Mol Cancer ， 2018 ， 17 （ 1 ）： 147 .

Lawson J ， Dickman C ， Towle R ， et al . Extracellular vesicle secretion of miR-142-3p from lung adenocarcinoma cells induces tumor promoting changes in the stroma through cell-cell communication [J ] . Mol Carcinog ， 2019 ， 58 （ 3 ）： 376 - 387 .

Zheng GD ， Xu ZY ， Hu C ， et al . Exosomal miR-590-5p in serum as a biomarker for the diagnosis and prognosis of gastric cancer [J ] . Front Mol Biosci ， 2021 ， 8 ： 636566 .

Yang XZ ， Li F ， Ma J ， et al . Study on the relationship between the miRNA-centered CeRNA regulatory network and fatigue [J ] . J Mol Neurosci ， 2021 ， 71 （ 10 ）： 1967 - 1974 .

Taheri M ， Safarzadeh A ， Hussen BM ， et al . LncRNA/miRNA/mRNA network introduces novel biomarkers in prostate cancer [J ] . Cells ， 2022 ， 11 （ 23 ）： 3776 .

Kong XL ， Duan Y ， Sang YT ， et al . LncRNA-CDC6 promotes breast cancer progression and function as CeRNA to target CDC6 by sponging microRNA-215 [J ] . J Cell Physiol ， 2019 ， 234 （ 6 ）： 9105 - 9117 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effects of miR-629-5p on biological behavior of gastric cancer cells and identification of its target gene MTRF1L

Effect of hnRNPA2B1-mediated m⁶A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells

Research advances in mesenchymal stem cells and their exosomes in treatment of premature ovarian insufficiency

Research advances in liquid biopsy for bladder cancer

Related Author

He Qing

Li Zhaodong

Wu Xiaoling

Lu Wenwen

Zhou Haixia

Zhuang Jianbo

Wang Jiemin

Zhang Jing

Related Institution

Department of Gastroenterology and Hepatology，the Second Affiliated Hospital，Chongqing Medical University

Department of Gastroenterology，People’s Hospital of Suzhou New District

Department of Gastroenterology，Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Center for Reproductive Medicine，Department of Obstetrics and Gynecology，Peking University Third Hospital； State Key Laboratory of Female Fertility Promotion；National Clinical Research Center for Obstetrics and Gynecology；Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology

Department of Urology，Xiangya Hospital，Central South University/National Clinical Research Center for Geriatric Disorders

⁰