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评估 SPP1/骨桥蛋白表达作为他莫昔芬治疗乳腺癌复发的预测因子。

Evaluation of SPP1/osteopontin expression as predictor of recurrence in tamoxifen treated breast cancer.

机构信息

Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

School of Medical Sciences, Faculty of Medicine and Health, Örebro university, Örebro, Sweden.

出版信息

Sci Rep. 2020 Jan 29;10(1):1451. doi: 10.1038/s41598-020-58323-w.

DOI:10.1038/s41598-020-58323-w
PMID:31996744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6989629/
Abstract

Breast cancer patients treated with tamoxifen may experience recurrence due to endocrine resistance, which highlights the need for additional predictive and prognostic biomarkers. The glyco-phosphoprotein osteopontin (OPN), encoded by the SPP1 gene, has previously shown to be associated with poor prognosis in breast cancer. However, studies on the predictive value of OPN are inconclusive. In the present study, we evaluated tissue SPP1 mRNA and OPN protein expression as markers of recurrence in estrogen receptor- positive (ER+) breast cancer tissue. Tamoxifen- treated patients with recurrence or non-recurrence were selected using a matched case-control design. SPP1 mRNA expression was analysed using qPCR (n = 100) and OPN protein by immunohistochemistry (n = 116) using different antibodies. Odds ratios were estimated with conditional logistic regression. The SPP1 expression increased the risk of recurrence with an odds ratio (OR) of 2.50 (95% confidence interval [CI]; 1.30-4.82), after adjustment for tumour grade, HER 2 status and other treatments to OR 3.62 (95% CI; 1.45-9.07). However, OPN protein expression was not associated with risk of recurrence or with SPP1-gene expression, suggesting SPP1 mRNA a stronger prognostic marker candidate compared to tumor tissue OPN protein.

摘要

接受他莫昔芬治疗的乳腺癌患者可能因内分泌抵抗而复发,这凸显了需要额外的预测和预后生物标志物。糖基磷酸化蛋白骨桥蛋白(OPN)由 SPP1 基因编码,先前已显示与乳腺癌预后不良相关。然而,OPN 的预测价值研究尚无定论。在本研究中,我们评估了组织 SPP1 mRNA 和 OPN 蛋白表达作为雌激素受体阳性(ER+)乳腺癌组织复发的标志物。采用配对病例对照设计选择有或无复发的他莫昔芬治疗患者。使用 qPCR 分析 SPP1 mRNA 表达(n=100),并用不同抗体通过免疫组织化学分析 OPN 蛋白(n=116)。使用条件逻辑回归估计比值比。调整肿瘤分级、HER2 状态和其他治疗后,SPP1 表达增加了复发的风险,比值比(OR)为 2.50(95%置信区间[CI];1.30-4.82),但 OPN 蛋白表达与复发风险或 SPP1 基因表达无关,表明与肿瘤组织 OPN 蛋白相比,SPP1 mRNA 是一个更强的预后标志物候选物。

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