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血浆 microRNAs 作为早期胃癌早期检测的潜在新型生物标志物。

Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer.

机构信息

The Fifth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China.

The Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China.

出版信息

World J Gastroenterol. 2019 Apr 7;25(13):1580-1591. doi: 10.3748/wjg.v25.i13.1580.

Abstract

BACKGROUND

Early gastric cancer (EGC), compared with advanced gastric cancer (AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method.

AIM

To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs (miRNAs) in EGC and AGC and compared them with those in benign gastritis (BG).

METHODS

We examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, ()-negative gastritis (Control-1), and -positive atrophic gastritis (Control-2). To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups.

RESULTS

Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of -negative gastritis (Control-1) and -positive atrophic gastritis (Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs, miR-7641, miR-425-5p, miR-1180-3p and miR-122-5p, were used to effectively distinguish the Cancer group (EGC + AGC) from the Control group [area under the curve (AUC) = 0.799, 95% confidence interval (CI): 0.691-0.908, < 0.001]. Additionally, miR-425-5p, miR-24-3p, miR-1180-3p and miR-122-5p were utilized to distinguish EGC from the Control group (AUC = 0.829, 95%CI: 0.657-1.000, = 0.001). Moreover, the miR-24-3p expression level in EGC was lower than that in the AGC (AUC = 0.782, 95%CI: 0.571-0.993, = 0.029), and the miR-4632-5p expression level in EGC was significantly higher than that in AGC (AUC = 0.791, 95%CI: 0.574-1.000, = 0.024).

CONCLUSION

The differentially expressed circulatory plasma miR-425-5p, miR-1180-3p, miR-122-5p, miR-24-3p and miR-4632-5p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.

摘要

背景

早期胃癌(EGC)与晚期胃癌(AGC)相比,5 年生存率更高。然而,由于缺乏典型症状和难以诊断 EGC,因此没有有效的生物标志物用于检测 EGC,而胃镜检查是唯一的检测方法。

目的

通过分析 EGC 和 AGC 与良性胃炎(BG)之间差异表达的 microRNAs(miRNAs),为 EGC 提供特异性和敏感性更高的新生物标志物。

方法

我们通过 miRNA 芯片分析检测了 30 例 EGC、AGC 和 BG 患者血浆中差异表达的 miRNAs。然后,我们使用生物信息学分析和选择显著差异的 miRNAs。逆转录定量实时聚合酶链反应(RT-qPCR)在另 122 例患者中证实了这些 miRNAs 的相对转录水平,包括 EGC、AGC、(-)阴性胃炎(Control-1)和(-)阳性萎缩性胃炎(Control-2)患者。为了建立用于检测 EGC 血浆 miRNA 的诊断模型,我们选择了可以用于确定 EGC 和 AGC 与 Control-1 和 Control-2 以及所有其他组中的 EGC 的 miRNA。

结果

在发现组中三组的 miRNA 芯片表达谱中,30 个经确认的靶标预测中有 117 个 miRNA 表达异常,而 14 个被纳入潜在 miRNA。RT-qPCR 结果显示,在两组(-)阴性胃炎(Control-1)和(-)阳性萎缩性胃炎(Control-2)中,14 种潜在 miRNA 的表达谱无差异。因此,将这两组纳入 Control 组。四种类型的 miRNAs(miR-7641、miR-425-5p、miR-1180-3p 和 miR-122-5p)的组合可有效区分癌症组(EGC+AGC)与 Control 组[曲线下面积(AUC)=0.799,95%置信区间(CI):0.691-0.908,<0.001]。此外,miR-425-5p、miR-24-3p、miR-1180-3p 和 miR-122-5p 可用于区分 EGC 与 Control 组(AUC=0.829,95%CI:0.657-1.000,=0.001)。此外,EGC 中的 miR-24-3p 表达水平低于 AGC(AUC=0.782,95%CI:0.571-0.993,=0.029),而 EGC 中的 miR-4632-5p 表达水平明显高于 AGC(AUC=0.791,95%CI:0.574-1.000,=0.024)。

结论

差异表达的循环血浆 miR-425-5p、miR-1180-3p、miR-122-5p、miR-24-3p 和 miR-4632-5p 可作为 EGC 诊断的新潜在生物标志物。通过将胃镜检查与这些 miRNA 生物标志物联合使用,可以极大地促进 EGC 的预测和早期诊断,从而优化 EGC 的有效检测策略。然而,仍需要更大规模的人类实验来证实我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48e9/6452233/a56ed8592e43/WJG-25-1580-g001.jpg

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