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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

CREB3L1 as a potential biomarker predicting response of triple negative breast cancer to doxorubicin-based chemotherapy

Authors: Bray Denard, Sharon Jiang, Yan Peng, Jin Ye

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.
Literature
1.
Peng Y, Butt YM, Chen B, Zhang X, Tang P. Update on immunohistochemical analysis in breast lesions. Arch Pathol Lab Med. 2017;141(8):1033–51.CrossRefPubMed
2.
Rampurwala MM, Rocque GB, Burkard ME. Update on adjuvant chemotherapy for early breast cancer. Breast Cancer. 2014;8:125–33.PubMed
3.
Nabholtz J-MA, Reese DM, Lindsay M-A, Riva A. Docetaxel in the treatment of breast cancer: An update on recent studies. Semin Oncol. 2002;29(3):28–34.CrossRefPubMed
4.
Fisher B, Jeong J-H, Anderson S, Wolmark N. Treatment of axillary lymph node–negative, estrogen receptor–negative breast cancer: Updated findings from national surgical adjuvant breast and bowel project clinical trials. J Natl Cancer Inst. 2004;96(24):1823–31.CrossRefPubMed
5.
Kaufman PA. Paclitaxel and anthracycline combination chemotherapy for metastatic breast cancer. Semin Oncol. 1999;26:39–46.PubMed
6.
Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin Cardiomyopathy. Cardiology. 2010;115(2):155–62.CrossRefPubMed
7.
Patel AG, Kaufmann SH. How does doxorubicin work? eLife. 2012;1
8.
Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57:727–41.CrossRefPubMed
9.
10.
Denard B, Seemann J, Chen Q, Gay A, Huang H, Chen Y, Ye J. The membrane-bound transcription factor CREB3L1 is activated in response to virus infection to inhibit proliferation of virus-infected cells. Cell Host Microbe. 2011;10:65–74.CrossRefPubMedPubMedCentral
11.
Sivanand S, Peña-Llopis S, Zhao H, Kucejova B, Spence P, Pavia-Jimenez A, Yamasaki T, McBride DJ, Gillen J, Wolff NC, et al. A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma. Sci Transl Med. 2012;4(137):137ra175.CrossRef
12.
Denard B, Pavia-Jimenez A, Chen W, Williams NS, Naina H, Collins R, Brugarolas J, Ye J. Identification of CREB3L1 as a biomarker predicting doxorubicin treatment outcome. PLoS ONE. 2015;10(6):e0129233.CrossRefPubMedPubMedCentral
13.
Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue – a review. Diagn Pathol. 2014;9:221.CrossRefPubMedPubMedCentral
14.
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, et al. Measurement of Residual Breast Cancer Burden to predict survival after neoadjuvant chemotherapy. J clin Oncol. 2007;25(28):4414–22.CrossRefPubMed
15.
Han JS, Cao D, Molberg KH, Sarode VR, Rao R, Sutton LM, Peng Y. Hormone receptor status rather than HER2 status is significantly associated with increased Ki-67 and p53 expression in triple-negative breast carcinomas, and high expression of Ki-67 but not p53 Is significantly associated with axillary nodal metastasis in triple-negative and high-grade non–triple-negative breast carcinomas. Am J Clin Pathol. 2011;135(2):230–7.CrossRefPubMed
16.
17.
Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.CrossRefPubMed
18.
Chen Q, Denard B, Huang H, Ye J. Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive for Hepatitis C virus replication. J Virol. 2013;87(1):659–65.CrossRefPubMedPubMedCentral
19.
Rose M, Schubert C, Dierichs L, Gaisa NT, Heer M, Heidenreich A, Knüchel R, Dahl E. OASIS/CREB3L1 is epigenetically silenced in human bladder cancer facilitating tumor cell spreading and migration in vitro. Epigenetics. 2014;9(12):1626–40.CrossRefPubMed
20.
Steenbergen RDM, Ongenaert M, Snellenberg S, Trooskens G, van der Meide WF, Pandey D, Bloushtain-Qimron N, Polyak K, Meijer CJLM, Snijders PJF, et al. Methylation-specific digital karyotyping of HPV16E6E7-expressing human keratinocytes identifies novel methylation events in cervical carcinogenesis. J Pathol. 2013;231(1):53–62.CrossRefPubMed
21.
Ward AK, Mellor P, Smith SE, Kendall S, Just NA, Vizeacoumar FS, Sarker S, Phillips Z, Alvi R, Saxena A, et al. Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers. Breast Cancer Res. 2016;18:12.CrossRefPubMedPubMedCentral
22.
23.
Khan GN, Kim EJ, Shin TS, Lee SH. Azacytidine-induced chemosensitivity to doxorubicin in human breast cancer MCF7 Cells. Anticancer Res. 2017;37(5):2355–64.CrossRefPubMed
Metadata
Title
CREB3L1 as a potential biomarker predicting response of triple negative breast cancer to doxorubicin-based chemotherapy
Authors
Bray Denard
Sharon Jiang
Yan Peng
Jin Ye
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4724-8

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