血浆中的 miRNA-199a-3p 作为胃癌的潜在诊断生物标志物。

miRNA-199a-3p in plasma as a potential diagnostic biomarker for gastric cancer.

机构信息

Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

出版信息

Ann Surg Oncol. 2013 Dec;20 Suppl 3:S397-405. doi: 10.1245/s10434-012-2600-3. Epub 2012 Sep 7.

DOI:10.1245/s10434-012-2600-3

PMID:22956063

Abstract

BACKGROUND

MicroRNA (miRNA) has been shown the potential of cancer diagnosis. We investigated whether plasma miRNA expression could discriminate between patients with and without gastric cancer.

METHODS

This study was divided into three steps: (1) miRNA microarray profiling on plasma samples from 20 gastric cancer patients and 20 healthy controls; (2) miRNA selection by real-time qRT-PCR on 30 pairs of plasma from patients and controls; and (3) qRT-PCR validation on an independent set of plasma from 180 gastric cancer patients, 80 healthy controls, and 20 patients with gastric precancerous diseases.

RESULTS

Of the 959 human miRNAs analyzed by microarray, 37 up-regulated miRNAs and seven down-regulated miRNAs were found in gastric cancer plasma. Of the seven discrepant miRNAs validated on the plasma from 30 gastric cancer patients and 30 healthy controls, both miRNA-199a-3p and miRNA-151-5p were significantly elevated (p < 0.05) and were significantly reduced after surgery (p < 0.05) in gastric cancer patients. Further large-scale validation showed that these two miRNAs expressions in plasma were significantly higher in gastric cancer patients than healthy controls and patients with gastric precancerous diseases, respectively. However, only the expression of miRNA-199a-3p in plasma was significantly associated with tumor invasion and with lymph node metastasis and tumor, node, metastasis stage. This marker yielded an area under the receiver operating characteristic curve area of 0.837 with 80 % sensitivity and 74 % specificity in discriminating gastric cancer patients from healthy controls. In gastric cancer tissue, miRNA-199a-3p was expressed in the cytoplasm of tumor cells.

CONCLUSIONS

miRNA-199a-3p in plasma could be a novel potential diagnostic biomarker for gastric cancer detection.

摘要

背景

MicroRNA (miRNA) 已显示出用于癌症诊断的潜力。我们研究了血浆 miRNA 表达是否可以区分胃癌患者和非胃癌患者。

方法

本研究分为三个步骤：(1) 对 20 例胃癌患者和 20 例健康对照者的血浆样本进行 miRNA 微阵列分析；(2) 通过实时 qRT-PCR 对 30 对患者和对照者的血浆样本进行 miRNA 选择；以及(3) 在 180 例胃癌患者、80 例健康对照者和 20 例胃癌前病变患者的独立血浆样本中进行 qRT-PCR 验证。

结果

在通过微阵列分析的 959 个人类 miRNA 中，在胃癌血浆中发现 37 个上调 miRNA 和 7 个下调 miRNA。在对 30 例胃癌患者和 30 例健康对照者的血浆中验证的 7 个差异表达 miRNA 中，miRNA-199a-3p 和 miRNA-151-5p 均显著升高(p<0.05)，胃癌患者手术后明显降低(p<0.05)。进一步的大规模验证表明，这两种 miRNA 在血浆中的表达在胃癌患者中明显高于健康对照者和胃癌前病变患者。然而，只有 miRNA-199a-3p 在血浆中的表达与肿瘤浸润以及淋巴结转移和肿瘤、淋巴结、转移分期显著相关。该标志物在区分胃癌患者与健康对照者时，曲线下面积为 0.837，敏感性为 80%，特异性为 74%。在胃癌组织中，miRNA-199a-3p 表达在肿瘤细胞的细胞质中。