The Utility of SOX2 and AGR2 Biomarkers as Early Predictors of Tamoxifen Resistance in ER-Positive Breast Cancer Patients.

IF 1.6 Q4 ONCOLOGY
International Journal of Surgical Oncology Pub Date : 2021-09-15 eCollection Date: 2021-01-01 DOI:10.1155/2021/9947540
Yomna Zamzam, Yosra Abdelmonem Zamzam, Marwa Aboalsoud, Heba Harras
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引用次数: 3

Abstract

Background: Despite the undeniable benefit of tamoxifen therapy for ER-positive breast cancer patients, approximately one-third of those patients either do not respond to tamoxifen or develop resistance. Thus, it is a crucial step to identify novel, reliable, and easily detectable biomarkers indicating resistance to this drug.

Objective: The aim of this work is to explore SOX2 and AGR2 biomarker expression in the tumor tissue of ER-positive breast cancer patients in combination with the evaluation of serum AGR2 level of these patients in order to validate these biomarkers as early predictors of tamoxifen resistance.

Methods: This study was conducted on 224 ER-positive breast cancer patients. All patients were primarily subjected to serum AGR2 levelling by ELISA and their breast cancer tissue immunostained for SOX2 and AGR2. After 5 years of follow-up, the patients were divided into 3 groups: group 1 was tamoxifen sensitive and groups 2 and 3 were tamoxifen resistant. Time to failure of tamoxifen treatment was considered the time from the beginning of tamoxifen therapy to the time of discovery of breast cancer recurrence or metastases (in months).

Results: SOX2 and AGR2 biomarkers expression and serum AGR2 level were significantly higher in groups 2 and 3 in comparison to group 1, while the relationship between Her2 neu expression and Ki67 index in the 3 different groups was statistically nonsignificant. Lower SOX2 and AGR2 expression and low AGR2 serum levels in the studied patients of groups 2 and 3 were significantly associated with longer time-to-failure of tamoxifen treatment. According to the ROC curve, the combined use of studied markers validity was with a sensitivity of 100%, specificity of 96%, PPV 96%, and NPV 100% (p < 0.001; AUC: 0.984).

Conclusions: Integrated use of SOX2 and AGR2 biomarkers with serum AGR2 assay holds a promising hope for their future use as predictive markers for early detection of tamoxifen resistance in ER-positive breast cancer patients.

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SOX2和AGR2生物标志物作为er阳性乳腺癌患者他莫昔芬耐药的早期预测指标
背景:尽管三苯氧胺治疗ER阳性乳腺癌症患者具有不可否认的益处,但约三分之一的患者对三苯氧碱没有反应或出现耐药性。因此,识别新的、可靠的、易于检测的指示对该药物耐药性的生物标志物是至关重要的一步。目的:本工作的目的是结合对ER-阳性乳腺癌症患者血清AGR2水平的评估,探讨SOX2和AGR2生物标志物在肿瘤组织中的表达,以验证这些生物标志物作为他莫昔芬耐药性的早期预测因子。方法:对224例ER阳性乳腺癌症患者进行研究。所有患者首先通过ELISA进行血清AGR2水平测定,并对其癌症组织进行SOX2和AGR2免疫染色。经过5年的随访,患者被分为3组:第一组为三苯氧胺敏感组,第二组和第三组为三苯氧胺耐药性组。三苯氧胺治疗失败的时间被认为是从三苯氧碱治疗开始到发现乳腺癌症复发或转移的时间(以月为单位),而Her2-neu表达与Ki67指数之间的关系在3个不同组中无统计学意义。在第2组和第3组的研究患者中,较低的SOX2和AGR2表达以及较低的AGR2血清水平与三苯氧胺治疗失败的时间较长显著相关。根据ROC曲线,联合使用所研究的标志物的有效性具有100%的敏感性、96%的特异性、96%的PPV和100%的NPV(p<0.001;AUC:0.984)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
5
审稿时长
20 weeks
期刊介绍: International Journal of Surgical Oncology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of surgical oncology.
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