CREB3L1 as a potential biomarker predicting response of triple negative breast cancer to doxorubicin-based chemotherapy.
CREB3L1 as a potential biomarker predicting response of triple negative breast cancer to doxorubicin-based chemotherapy.
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DOI：
10.1186/s12885-018-4724-8
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发表时间：
2018-08-13
期刊：
影响因子：
3.8
通讯作者：
Ye J
中科院分区：
文献类型：
--
作者：
Denard B;Jiang S;Peng Y;Ye J
以阿霉素为基础的化疗是目前三阴性乳腺癌（TNBC）最常用的治疗方法，但由于在化疗开始前缺乏一种生物标志物来识别反应性患者，因此反应率不高。我们已经证明，阿霉素通过一种名为CREB3L1 （cAMP反应元件结合蛋白3-like 1）的转录因子的蛋白水解激活来抑制癌细胞的增殖，并且当癌细胞在体外培养或在小鼠体内建立异种移植肿瘤时，CREB3L1在癌细胞中的表达是其对阿霉素敏感性的关键决定因素。本研究的目的是确定是否可以将TNBC患者肿瘤细胞中的CREB3L1表达作为预测阿霉素化疗结果的生物标志物。我们对18名三阴癌患者在接受阿霉素化疗前的乳房核心活检组织样本进行了回顾性分析。通过免疫组化分析癌细胞中CREB3L1的表达，并使用免疫反应评分（Immunoreactive Score， IRS）进行量化。化疗结果用残余癌负荷（RCB）系统来衡量。CREB3L1在对阿霉素化疗有反应的TNBC （RCB 0-2级）中的表达水平显著高于耐药肿瘤（RCB 3级）（未配对双尾t检验，p = 0.0005； 95%置信水平下统计能力为99.8）。所有表达较高水平CREB3L1 （IRS 4-12）的癌症对基于阿霉素的化疗有反应，而所有抵抗治疗的癌症表达较低水平CREB3L1 （IRS 0-3）。这些结果表明，CREB3L1表达水平可以作为一种生物标志物，用于识别更有可能从阿霉素化疗中获益的TNBC患者。
Doxorubicin-based chemotherapy is currently the most frequently used treatment for triple negative breast cancer (TNBC), yet the response rate is not high due to the lack of a biomarker allowing identification of responsive patients before the chemotherapy is initiated. We have demonstrated that doxorubicin inhibits proliferation of cancer cells through proteolytic activation of a transcription factor called CREB3L1 (cAMP response element binding protein 3-like 1), and that CREB3L1 expression in cancer cells is a key determinant of their sensitivity to doxorubicin when they are cultured in vitro or established as xenograft tumors in mice. The purpose of this study is to determine whether CREB3L1 expression in tumor cells of TNBC patients can be established as a biomarker to predict outcomes of doxorubicin-based chemotherapy. We performed a retrospective analysis on breast core biopsy tissue samples taken from 18 TNBC patients before they were treated with doxorubicin-based chemotherapy. CREB3L1 expression in the cancer cells was analyzed by immunohistochemistry and quantified using the Immunoreactive Score (IRS). Outcomes of the chemotherapy were measured by the residual cancer burden (RCB) system. CREB3L1 expression levels in TNBC responsive to doxorubicin-based chemotherapy (RCB class 0-2) were significantly higher than that in resistant cancers (RCB class 3) (unpaired two-tailed t test, p = 0.0005; Statistical power 99.8 at 95% confidence level). All cancers expressing higher levels of CREB3L1 (IRS 4-12) responded to doxorubicin-based chemotherapy, whereas all cancers resisting the treatment expressed lower levels of CREB3L1 (IRS 0-3). These results suggest that CREB3L1 expression level may be used as a biomarker to identify TNBC patients who are more likely to benefit from doxorubicin-based chemotherapy.
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影响因子：
7.7
作者：
Denard B;Lee C;Ye J
通讯作者：
Ye J
影响因子：
2.6
作者：
Fedchenko N;Reifenrath J
通讯作者：
Reifenrath J
影响因子：
45.3
作者：
Liedtke, Cornelia;Mazouni, Chafika;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
将CREB3L1鉴定为预测阿霉素治疗结果的生物标志物。
影响因子：
3.7
作者：
Denard B;Pavia-Jimenez A;Chen W;Williams NS;Naina H;Collins R;Brugarolas J;Ye J
通讯作者：
Ye J
DOI：
10.1186/s13058-016-0672-x
发表时间：
2016-01-25
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Ward AK;Mellor P;Smith SE;Kendall S;Just NA;Vizeacoumar FS;Sarker S;Phillips Z;Alvi R;Saxena A;Vizeacoumar FJ;Carlsen SA;Anderson DH
通讯作者：
Anderson DH