从血清外泌体 microRNAs 中鉴定慢性萎缩性胃炎的非侵入性生物标志物。
Identification of non-invasive biomarkers for chronic atrophic gastritis from serum exosomal microRNAs.
机构信息
The First Affiliated Hospital of Guangdong Pharmaceutical University, No.19 Nonglinxia Road, Guangzhou, 510080, Guangdong Province, China.
Guangzhou University of Chinese Medicine, No.12 Jichang Road, Guangzhou, 510405, Guangdong Province, China.
出版信息
BMC Cancer. 2019 Feb 8;19(1):129. doi: 10.1186/s12885-019-5328-7.
BACKGROUND
Serum exosomal microRNAs (miRNAs) have been suggested as novel biomarkers for various diseases, especially gastric cancer (GC). But circulating biomarkers for Chronic atrophic gastritis (CAG) which is defined as precancrerous lesions of GC remain largely elusive. To investigate serum exosomal miRNAs that are differently expressed in CAG patients and Chronic nonatrophic gastritis (CNAG) may be helpful for its diagnosis and therapy.
METHODS
Patients were recruited according to the diagnosis and exclusioncriteria. RNA was extracted from serum exosomes of 30 CAG and 30 CNAG patients. The miRNA expression profiles were analyzed by next generation sequencing and were validated by qRT-PCR. Receiver operating characteristic (ROC) analysis has been used to evaluate the diagnostic value.
RESULTS
30 CAG patients and 30 CNAG patients were recruited in our study. sRNA-seq results showed that hsa-miR-3591-3p, - 122-3p, and - 122-5p of the top 10 miRNAs (hsa-miR-148a-3p, - 122-3p, - 486-3p, -451a, - 122-5p, - 3591-3p, - 486-5p, -151a-3p, -92a-3p, -320a) were significantly upregulated in exosomes from CAG patients versus those from CNAG patients, but hsa-miR-451a, -151a-3p, and -92a-3p were significantly downregulated. Furthermore, qRT-PCR analysis confirmed that hsa-miR-122-5p and hsa-miR-122-3p were significantly upregulated in CAG samples, but hsa-miR-122-3p hadnot a steable expression. ROC curves showed that the AUC for hsa-miR-122-5p was 0.67 (95% CI 0.52-0.82, SE 62%, SP 86%). A sum of the four miRNAs (panel 1, hsa-miR-122-5p, -451a, -151a-3p, and -92a-3p) did not significantly improve the diagnostic potential (AUC 0.63, 95% CI 0.47 to 0.78). Correlation analysis showed that the expression of hsa-miR-122-5p differed significantly between patients based on atrophic (Moderate atrophic vs. Absent, P value was 0.036.) and IM (compare moderate-severe, absent and mild P values were 0.001 and 0.014, respectively). However, there were no differences between groups based on age, gender, dysplasia, or chronic or active inflammation.
CONCLUSION
These results suggested that hsa-miR-122-5p in serum exosomes might serve as a potential biomarker for CAG diagnosis.
TRIAL REGISTRATION
Chinese Clinical Trial Registy ( ChiCTR-IOR-16008027 , Date of Registration:2016-03-01).
背景
血清外泌体 microRNAs（miRNAs）已被认为是各种疾病，尤其是胃癌（GC）的新型生物标志物。但是，用于慢性萎缩性胃炎（CAG）的循环生物标志物仍然很大程度上难以捉摸，CAG 被定义为 GC 的癌前病变。研究在 CAG 患者中差异表达的血清外泌体 miRNAs，可能有助于其诊断和治疗。
方法
根据诊断和排除标准招募患者。从 30 例 CAG 和 30 例 CNAG 患者的血清外泌体中提取 RNA。通过下一代测序分析 miRNA 表达谱，并通过 qRT-PCR 进行验证。接受者操作特征（ROC）分析用于评估诊断价值。
结果
我们的研究纳入了 30 例 CAG 患者和 30 例 CNAG 患者。sRNA-seq 结果显示，与 CNAG 患者相比，CAG 患者外泌体中 top10 miRNAs（hsa-miR-148a-3p、-122-3p、-486-3p、-451a、-122-5p、-3591-3p、-486-5p、-151a-3p、-92a-3p、-320a）中的 hsa-miR-3591-3p、-122-3p 和-122-5p 显著上调，但 hsa-miR-451a、-151a-3p 和-92a-3p 显著下调。此外，qRT-PCR 分析证实 hsa-miR-122-5p 和 hsa-miR-122-3p 在 CAG 样本中显著上调，但 hsa-miR-122-3p 表达不稳定。ROC 曲线显示 hsa-miR-122-5p 的 AUC 为 0.67（95%CI 0.52-0.82，SE 62%，SP 86%）。四个 miRNAs 的总和（panel1，hsa-miR-122-5p、-451a、-151a-3p 和-92a-3p）并没有显著提高诊断潜力（AUC 0.63，95%CI 0.47 至 0.78）。相关性分析表明，基于萎缩（中度萎缩与无，P 值为 0.036）和 IM（中度-重度、无和轻度相比，P 值分别为 0.001 和 0.014），hsa-miR-122-5p 的表达在患者之间存在显著差异。然而，在年龄、性别、发育不良或慢性或活动性炎症方面，各组之间没有差异。
结论
这些结果表明，血清外泌体中的 hsa-miR-122-5p 可能作为 CAG 诊断的潜在生物标志物。
临床试验注册
中国临床试验注册中心（ChiCTR-IOR-16008027，注册日期：2016-03-01）。
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