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卵巢癌患者外周血中的新型生物标志物:miR-16-5p、miR-17-5p 和 miR-638 高表达水平。

New biomarkers in peripheral blood of patients with ovarian cancer: high expression levels of miR-16-5p, miR-17-5p, and miR-638.

机构信息

Division of Cancer Genetics, Department of Basic Oncology, Oncology Institute, Istanbul University, Fatih , 34093, Istanbul, Turkey.

Health Sciences Institute, Istanbul University, Beyazıt/Fatih, 34452, Istanbul, Turkey.

出版信息

Arch Gynecol Obstet. 2022 Jan;305(1):193-201. doi: 10.1007/s00404-021-06138-z. Epub 2021 Aug 9.

DOI:10.1007/s00404-021-06138-z
PMID:34370073
Abstract

OBJECTIVES

Ovarian cancer is one of the most fatal gynecologic malignities. miR-16-5p, miR-17-5p, and miR-638 genes were found to have been associated with ovarian cancer in accordance with the data obtained from the previous microarray research performed by Tuncer et al. (J Ovarian Res 13(1):99, 2020). The expression levels of these miRNAs in the peripheral blood samples of 142 ovarian cancer patients, and 97 healthy controls were investigated for performing the validation, and to identify whether these genes were the possible biomarkers to be used in the early diagnosis of high-risk ovarian cancer patients, and in the prognosis of patients.

METHODS

The miRNA expression analysis was performed using the miRNA-specific cDNA synthesis, and real-time PCR methods following the RNA isolation from the peripheral blood lymphocytes.

RESULTS

miR-16-5p, miR-17-5p, and miR-638 miRNA gene expression levels were found to have twofold higher expression levels in patient groups compared with the gene expression levels in healthy controls, and were statistically significant (p < 0.05). In addition, the comparison of the miRNA expression levels with the clinical data of patients showed that there was a significant difference with smoking history and the increased expression level of miR-17-5 (p: 0.007). There was a significant difference between the increased expression level of miR-638 with the locally advanced stage, and abdominal/pelvic metastatic patients (p: 0.03).

CONCLUSIONS

The obtained data suggest that miR-16-5p, miR-17-5p, and miR-638 molecules might be the noninvasive biomarkers in identifying the ovarian cancer. However, the investigation and monitoring of the changeability of these biomarkers in benign ovarian diseases, and during the treatment must be performed in future studies for identifying the accurate diagnostic, and prognostic features of miRNAs.

摘要

目的

卵巢癌是最致命的妇科恶性肿瘤之一。根据 Tuncer 等人之前进行的微阵列研究的数据,发现 miR-16-5p、miR-17-5p 和 miR-638 基因与卵巢癌有关。研究人员检测了 142 名卵巢癌患者和 97 名健康对照者外周血样本中这些 miRNA 的表达水平,以进行验证,并确定这些基因是否是高危卵巢癌患者早期诊断和患者预后的可能生物标志物。

方法

采用 miRNA 特异性 cDNA 合成和实时 PCR 方法,从外周血淋巴细胞中提取 RNA 进行 miRNA 表达分析。

结果

与健康对照组相比,患者组中 miR-16-5p、miR-17-5p 和 miR-638 基因的表达水平高出两倍,且具有统计学意义(p<0.05)。此外,miRNA 表达水平与患者的临床资料比较显示,吸烟史和 miR-17-5 表达水平升高有显著差异(p=0.007)。miR-638 表达水平升高与局部晚期和腹部/盆腔转移患者有显著差异(p=0.03)。

结论

研究结果表明,miR-16-5p、miR-17-5p 和 miR-638 分子可能是非侵入性生物标志物,用于识别卵巢癌。然而,必须在未来的研究中进一步调查和监测这些生物标志物在良性卵巢疾病和治疗过程中的可变性,以确定 miRNA 的准确诊断和预后特征。

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