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乳腺癌复发的潜在蛋白质标志物:一项回顾性队列研究。

Potential protein markers for breast cancer recurrence: a retrospective cohort study.

作者信息

He Chunyan, Plattner Rina, Rangnekar Vivek, Zhou Binhua, Liu Chunming, Stewart Rachel L, Huang Bin, Wang Chi, Tucker Thomas C

机构信息

Markey Cancer Center, University of Kentucky, 744 Rose Street, Combs 206, Lexington, KY, 40536, USA.

Department of Internal Medicine, Division of Medical Oncology, College of Medicine, University of Kentucky, Lexington, KY, USA.

出版信息

Cancer Causes Control. 2019 Jan;30(1):41-51. doi: 10.1007/s10552-018-1099-8. Epub 2018 Nov 28.

Abstract

BACKGROUND

We evaluated five key proteins involved in various cancer-related pathways and assessed their relation to breast cancer recurrence.

METHODS

We used the Kentucky Cancer Registry to retrospectively identify primary invasive breast cancer cases (n = 475) that were diagnosed and treated at University of Kentucky Medical Center between 2000 and 2007. Breast cancer recurrence was observed in 62 cases during the 5-year follow-up after diagnosis. Protein expression or activity level was analyzed from surgery tissue using immuno-histochemical assays.

RESULTS

Compared to ER+/PR+/HER2- patients without recurrence, those with recurrence had higher TWIST expression (p = 0.049) but lower ABL1/ABL2 activity (p = 0.003) in primary tumors. We also found that triple-negative breast cancer patients with recurrence had higher SNAI1 expression compared to those without recurrence (p = 0.03). After adjusting for potential confounders, the higher ABL1/ABL2 activity in primary tumors was associated with a decreased risk of recurrence (OR 0.72, 95% CI 0.85-0.90) among ER+/PR+/HER2- patients. In addition, among patients with recurrence we observed that the activity level of ABL1/ABL2 was significantly increased in recurrent tumors compared to the matched primary tumors regardless of the subtype (p = 0.013).

CONCLUSIONS

These findings provide evidence that the expression/activity level of various proteins may be differentially associated with risk of recurrence of breast tumor subtypes.

摘要

背景

我们评估了参与各种癌症相关通路的五种关键蛋白,并评估了它们与乳腺癌复发的关系。

方法

我们利用肯塔基癌症登记处回顾性地识别2000年至2007年间在肯塔基大学医学中心诊断和治疗的原发性浸润性乳腺癌病例(n = 475)。在诊断后的5年随访期间,观察到62例乳腺癌复发。使用免疫组织化学分析从手术组织中分析蛋白表达或活性水平。

结果

与无复发的ER+/PR+/HER2-患者相比,复发患者的原发性肿瘤中TWIST表达较高(p = 0.049),但ABL1/ABL2活性较低(p = 0.003)。我们还发现,复发的三阴性乳腺癌患者与未复发患者相比,SNAI1表达较高(p = 0.03)。在调整潜在混杂因素后,原发性肿瘤中较高的ABL1/ABL2活性与ER+/PR+/HER2-患者复发风险降低相关(OR 0.72,95%CI 0.85 - 0.90)。此外,在复发患者中,我们观察到无论亚型如何,与匹配的原发性肿瘤相比,复发肿瘤中ABL1/ABL2的活性水平显著升高(p = 0.013)。

结论

这些发现提供了证据,表明各种蛋白的表达/活性水平可能与乳腺肿瘤亚型的复发风险存在差异关联。

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