血清外泌体miRNAs联合CA72-4在胃癌诊断中的价值分析

孙婧悦; 王啸

doi:10.12354/j.issn.1000-8179.2022.20211798

血清外泌体miRNAs联合CA72-4在胃癌诊断中的价值分析

doi: 10.12354/j.issn.1000-8179.2022.20211798

孙婧悦^1,,
王啸^2, ,

1.
苏州大学附属第一医院肿瘤科（苏州市215006）
2.
苏州大学附属第二医院骨外科

基金项目: 本文课题受国家自然科学基金项目（编号：82003473）资助

详细信息

作者简介:
孙婧悦：专业方向为胃肠道肿瘤的临床及基础研究

通讯作者:
王啸 873417000@qq.com

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出版历程
- 收稿日期: 2021-11-30
- 录用日期: 2022-04-24
- 网络出版日期: 2022-06-27

Serum exosomal miRNAs combined with CA72-4 as biomarkers for diagnosis of gastric cancer

Jingyue Sun^1
,,
Xiao Wang^{2
, ,}

1.
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
2.
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

Funds: This work was supported by the National Natural Science Foundation of China (No. 82003473)

More Information

Corresponding author: Xiao Wang; E-mail: 873417000@qq.com

摘要

摘要: 目的筛选胃癌患者及健康人血清外泌体miRNAs，探究miRNAs联合肿瘤标记物在胃癌诊断中的价值。方法选取2020年4月至2021年4月在苏州大学附属第一医院确诊胃癌的46例患者为胃癌组，同期20例健康体检者为对照组，收集两组血清标本，行血清外泌体miRNAs测序，筛选并验证差异性表达的miRNAs，将验证后的miRNAs表达水平、肿瘤标志物数值与胃癌诊断行Spearman相关分析，并绘制受试者工作特征（receiver operating characteristic ，ROC）曲线，分别分析外泌体miRNAs、CA72-4及两者联合在胃癌诊断中的价值。结果两组血清外泌体共筛选出376个差异表达的miRNAs，经q-PCR验证，仅4个miRNAs差异具有统计学意义，采用ROC曲线判断外泌体miRNAs在胃癌诊断中的效能：miR-1323、miR-26a-5p、miR-202-3p、miR-96-5p诊断胃癌的曲线下面积（area under curve，AUC）分别为0.908、0.815、0.570、0.547，灵敏度分别为71.7%、67.4%、30.4%、19.6%，特异度分别100%、85.0%、90.0%、100%。Spearman相关分析结果提示：miR-26a-5p、miR-1323和CA72-4与胃癌诊断相关，ROC曲线显示：miR-26a-5p、miR-1323和CA72-4三者联合诊断的曲线下面积为0.967，高于三者单独诊断效能，其灵敏度和特异度分别为87.0%、100%。结论联合检测血清外泌体miR-26a-5p、miR-1323和CA72-4的表达水平，在胃癌诊断中具有潜在价值。
- 胃癌 /
- 外泌体miRNAs /
- 诊断
Abstract: Objective To investigate the role of serum exosomal miRNAs in combination with tumor markers in the diagnosis of patients with gastric cancer. Methods A total of 46 patients diagnosed with gastric cancer in The First Affiliated Hospital of Soochow University from April 2020 to April 2021 were selected as the gastric cancer group, and 20 healthy individuals who underwent physical examination during the same period were selected as the control group. Serum samples from the two groups were collected, serum exosomal miRNAs were sequenced, and differentially expressed miRNAs were screened and verified. Spearman correlation analysis was performed between the verified miRNAs expression level, tumor marker value, and diagnosis of gastric cancer. The receiver operating characteristic (ROC) curve was drawn to analyze the value of exosomal miRNAs, CA72-4, and their combination in the diagnosis of gastric cancer. Results A total of 376 differentially expressed miRNAs were screened from serum exosomes of the two groups. After qRT-PCR verification, only 4 miRNAs were found to be statistically significant. ROC curve was used to determine the efficacy of miRNAs in the diagnosis of gastric cancer. The areas under the curve (AUC) for miR-1323, miR-26a-5p, miR-202-3p, and miR-96-5p were 0.908, 0.815, 0.570, and 0.547, respectively, the sensitivities were 71.7%, 67.4%, 30.4%, and 19.6%, respectively, and the specificities were 100%, 85.0%, 90.0%, and 100%, respectively. Spearman correlation analysis showed that miR-26a-5p, miR-1323, and CA72-4 correlated positively with the diagnosis of gastric cancer. ROC curve analysis showed that the AUC for the combined diagnosis of miR-26a-5p, miR-1323, and CA72-4 was 0.967, which is higher than the diagnostic efficiency of the three alone, and their sensitivity and specificity were 87.0% and 100%, respectively. Conclusions Combined detection of the expression levels of serum exosomal miR-26a-5p, miR-1323, and CA72-4 improves the diagnosis of gastric cancer.
- gastric cancer /
- exosomal miRNAs /
- diagnosis

HTML全文

图 1 血清外泌体鉴定

A：透射电镜下外泌体形态；B：Western blot检测外泌体特异蛋白表达

下载: 全尺寸图片幻灯片

图 2 胃癌组与对照组血清外泌体miRNAs测序分析

A：两组血清外泌体差异性miRNAs聚类分析；B：胃癌组血清外泌体中上下调倍数最具差异的10个miRNAs及其差异倍数

下载: 全尺寸图片幻灯片

图 3 外泌体miRNAs在胃癌组和对照组血清中表达量的散点图

下载: 全尺寸图片幻灯片

图 4 血清外泌体miRNAs诊断胃癌的ROC曲线

A：miR-1323；B：miR-26a-5p；C：miR-202-3p；D：miR-96-5p

下载: 全尺寸图片幻灯片

图 5 CA72-4以及外泌体miR-1323、miR-26a-5p联合CA72-4诊断胃癌的ROC曲线

A：CA72-4；B：外泌体miR-1323、miR-26a-5p联合CA72-4

下载: 全尺寸图片幻灯片

表 1 miRNAs引物序列

miRNAs	正向引物序列（5'～3'）
hsa-miR-1323	TCAAAACTGAGGGGCATTTTC
hsa-miR-26a-5p	UCCAUAAAGUAGGAAACACUACA
hsa-miR-202-3p	AGAGGTATAGGGCATGGGAA
hsa-miR-96-5p	ACGATGCACCTGTACGATCA
hsa-miR-1246	TGAAGTAGGACTGGGCAGAGA

下载: 导出CSV

表 2 Spearman相关分析

项目	相关系数	P
CEA	0.048	0.704
CA72-4	0.460	<0.001
miR-96-5p	0.075	0.548
miR-202-3p	0.111	0.376
miR-26a-5p	0.502	<0.001
miR-1323	0.649	<0.001
CA199	0.164	0.189

下载: 导出CSV

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