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下调激肽释放酶相关肽 5(KLK5)在乳腺癌患者中的表达:用于鉴别诊断乳腺病变的生物标志物。

Down-regulation of kallikrein-related peptidase 5 (KLK5) expression in breast cancer patients: a biomarker for the differential diagnosis of breast lesions.

机构信息

Department of Biochemistry and Molecular Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece.

出版信息

Clin Proteomics. 2011 May 31;8(1):5. doi: 10.1186/1559-0275-8-5.

Abstract

BACKGROUND

Kallikrein-related peptidase 5 (KLK5) is a secreted trypsin-like protease of the KLK family, encoded by the KLK5 gene. KLK5 has been found to cleave various extracellular matrix components, as well as to activate several other KLK proteases, triggering the stimulation of tissue microenvironment proteolytic cascades.

MATERIAL AND METHODS

KLK5 expression levels were quantified in 102 cancerous and benign breast tissue specimens, obtained by randomly chosen patients, using RT-qPCR assay. Subsequently, advanced biostatistics were applied in order to analyze the KLK5 expression profile in the two patients' cohorts and also to evaluate its clinical significance for the discrimination of breast tumors.

RESULTS

A statistically significant (p < 0.001) down-regulation of the KLK5 expression levels were observed in the malignant specimens compared to the benign ones. Logistic regression and ROC curve analysis revealed the significant (p < 0.001) and the independent (p < 0.001) value of the KLK5 expression quantification, for the discrimination of the malignant from the benign mammary gland biopsies. Moreover, KLK5 expression levels correlate with the pre-menopausal status (p < 0.005) as well as the ER-negative staining (p = 0.028) of women with breast cancer.

CONCLUSIONS

The quantification of KLK5 expression in breast tissue biopsies may be considered as a novel and independent biomarker for the differential diagnosis between malignant and benign tumors of the mammary gland.

摘要

背景

激肽释放酶相关肽酶 5(KLK5)是 KLK 家族的一种分泌型胰蛋白酶样蛋白酶,由 KLK5 基因编码。KLK5 已被发现可切割各种细胞外基质成分,并激活其他几种 KLK 蛋白酶,从而触发组织微环境蛋白水解级联的刺激。

材料与方法

使用 RT-qPCR 检测随机选择的 102 例癌性和良性乳腺组织标本中的 KLK5 表达水平。随后,应用高级生物统计学方法分析两个患者队列中的 KLK5 表达谱,并评估其对乳腺癌鉴别诊断的临床意义。

结果

与良性标本相比,恶性标本中 KLK5 表达水平存在统计学显著(p < 0.001)下调。逻辑回归和 ROC 曲线分析显示 KLK5 表达定量对恶性与良性乳腺活检的鉴别具有显著(p < 0.001)和独立(p < 0.001)的价值。此外,KLK5 表达水平与女性乳腺癌的绝经前状态(p < 0.005)以及 ER 阴性染色(p = 0.028)相关。

结论

在乳腺组织活检中定量 KLK5 表达可被视为鉴别乳腺良恶性肿瘤的一种新的独立生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ae/3167201/633fcaa820d5/1559-0275-8-5-1.jpg

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