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山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (2): 43-50.doi: 10.6040/j.issn.1671-7554.0.2024.0650

• 临床医学 • 上一篇    下一篇

粪便miRNA对结直肠进展期腺瘤无创筛查的临床价值

崔倩倩1,李金鹏1,吴豫丹1,侯志平2,孙玮螺3,崔盼盼3,何培元3   

  1. 1.承德医学院研究生学院, 河北 承德 067000;2.承德医学院基础医学院, 河北 承德 067000;3.承德医学院附属医院消化内科, 河北 承德 067000
  • 出版日期:2025-03-10 发布日期:2025-03-07
  • 通讯作者: 何培元. E-mail:peiyuanhe@163.com
  • 基金资助:
    河北省省级科技计划资助项目(203777106D);河北省科学技术厅重点研发项目(21377791D);河北省高等学校科学技术研究项目(ZD2022124);河北省医学科学研究课题(20231365);河北省政府资助优秀人才项目;承德医学院重点学科资助-内科学

Clinical value of fecal miRNA for non-invasive screening of advanced colorectal adenomas

CUI Qianqian1, LI Jinpeng1, WU Yudan1, HOU Zhiping2, SUN Weiluo3, CUI Panpan3, HE Peiyuan3   

  1. 1. Graduate School, Chengde Medical University, Chengde 067000, Hebei, China;
    2. Department of Basic Medical Science, Chengde Medical University, Chengde 067000, Hebei, China;
    3. Department of Gastroenterology, Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China
  • Online:2025-03-10 Published:2025-03-07

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摘要： 目的 筛选粪便中与结直肠进展期腺瘤发生相关的microRNAs(miRNAs),评估其在进展期腺瘤筛查及诊断中的临床价值。 方法 选取2022年6月至2023年12月承德医学院附属医院收治的110例结直肠癌患者(结直肠癌组)和94例进展期腺瘤患者(进展期腺瘤组),另选取80例健康体检者(对照组)。送检5例结直肠癌患者癌组织与癌旁组织进行二代测序发现异常表达miRNAs;收集20例健康体检者和30例结直肠癌患者粪便样本,采用实时荧光定量PCR(quantitative real-time PCR, qRT-PCR)法对异常表达miRNAs进行检测,以获得粪便异常miRNA;将结直肠癌组、进展期腺瘤组和对照组按照7:3比例随机分为训练队列和验证队列,采用qRT-PCR法对训练队列和验证队列中粪便异常miRNA表达进行检测,并通过受试者工作特征(receiver operating characteristic, ROC)曲线评估miR-29a-3p的筛查及诊断效能。为验证miR-29a-3p的筛查和诊断效能,将同期接受结肠镜检查的3 039例受试者作为观察组,必要时检查病理,计算进展期腺瘤检出率;另选取81例受试者作为筛查组,先检测粪便miR-29a-3p,再检查结肠镜及必要的病理学,计算粪便miR-29a-3p升高者进展期腺瘤检出率。采用χ2检验对观察组和筛查组检出率进行比较。 结果 miRNA组学检测发现5个差异表达的miRNAs(let-7c-5p、miR-203a-3p、miR-122-5p、miR-29a-3p、miR-92b-3p);通过训练队列证实,miR-29a-3p在进展期腺瘤组粪便中明显上调(P<0.05),粪便miR-29a-3p联合粪便隐血试验、性别及吸烟史用于进展期腺瘤诊断时ROC曲线下面积(area under curve, AUC)为0.840。通过验证队列进一步证实,miR-29a-3p在进展期腺瘤组粪便中高表达(P<0.05),粪便miR-29a-3p联合粪便隐血试验、性别及吸烟史可用于进展期腺瘤诊断(AUC值为0.807)。以粪便miR-29a-3p升高作为筛查指标的筛查组进展期腺瘤的结肠镜检出率为39.2%,与观察组差异有统计学意义(P<0.05)。 结论 miR-29a-3p在进展期腺瘤组粪便中表达显著增高,粪便miR-29a-3p与粪便隐血试验、性别和吸烟史联合构建的预测模型对进展期腺瘤筛查和诊断有一定的临床应用价值。

关键词: 进展期腺瘤, 结直肠癌, 粪便, 诊断, 生物标志物, microRNA-29a-3p

Abstract: Objective To screen out the candidate fecal microRNAs(miRNAs)that play a crucial role in the occurrence of advanced adenoma and evaluate their clinical value in the screening and diagnosis of advanced adenoma. Methods From June 2022 to December 2023, 110 patients with colorectal cancer treated at the Affiliated Hospital of Chengde Medical University were selected as the colorectal cancer group, 94 patients with advanced adenoma as the advanced adenoma group, and 80 healthy individuals undergoing physical examinations as the control group. Five colorectal cancer patients cancerous and adjacent tissues were sequenced using next-generation sequencing to identify abnormally expressed miRNAs. Quantitative real-time PCR(qRT-PCR)was used to detect the expression of abnormally expressed miRNAs in the faeces of 30 patients in the colorectal cancer group and 20 in the control group to obtain abnormal miRNAs in faeces. The colorectal cancer group, advanced adenoma group, and control group were randomly divided into a training cohort and a validation cohort in a 7∶3 ratio. qRT-PCR was used to detect the expression of abnormal miRNAs in faeces in both cohorts, and the screening and diagnostic efficacy of miR-29a-3p was evaluated using the receiver operating characteristic(ROC)curve. To verify the screening and diagnostic efficacy of miR-29a-3p, 3,039 subjects who underwent colonoscopy during the same period were used as the observation group, with direct colonoscopy and pathological examination when necessary to calculate the detection rate of advanced adenomas. Eighty-one subjects were used as the screening group, with faecal miR-29a-3p detection followed by colonoscopy and pathology if necessary,to calculate the detection rate of advanced adenomas in those with elevated faecal miR-29a-3p. The chi-squared test was used to compare the detection rates of the observation and screening groups. Results Five miRNAs(let-7c-5p,miR-203a-3p,miR-122-5p,miR-29a-3p,miR-92b-3p)were significantly higher in cancer tissues than adjacent tissues.Through the training cohort, it was confirmed that miR-29a-3p was significantly upregulated in feces of the advanced adenoma group(P<0.05), and the area under the ROC curve(AUC)for the diagnosis of advanced adenomas using faecal miR-29a-3p in combination with faecal occult blood test, gender and smoking history was 0.840. Further confirmation by the validation cohort showed that miR-29a-3p was highly expressed in faeces of the advanced adenoma group(P<0.05), and the combination of faecal miR-29a-3p with fecal occult blood test, gender and smoking history could be used for the diagnosis of advanced adenomas(AUC=0.807). The colonoscopy detection rate of advanced adenomas in the screening group using elevated fecal miR-29a-3p as a screening indicator was 39.2%, which was statistically different from the observation group(P<0.05). Conclusion miR-29a-3p is significantly upregulated in feces of advanced adenoma patients, and fecal miR-29a-3p has a high clinical diagnostic value for advanced adenoma.

Key words: Advanced adenomas, Colorectal cancer, Faeces, Diagnosis, Biomarker, microRNA-29a-3p

中图分类号: 

  • R735.3
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