Journal Article
. 2019 May; 23(8):4980-4990.
doi: 10.1111/jcmm.14338.

An estrogen receptor (ER)-related signature in predicting prognosis of ER-positive breast cancer following endocrine treatment

Jianing Tang 1 Qiuxia Cui 1 Dan Zhang 2 Xing Liao 1 Jian Zhu 1 Gaosong Wu 1 
  • PMID: 31124293
  •     39 References
  •     9 citations


Quite a few estrogen receptor (ER)-positive breast cancer patients receiving endocrine therapy are at risk of disease recurrence and death. ER-related genes are involved in the progression and chemoresistance of breast cancer. In this study, we identified an ER-related gene signature that can predict the prognosis of ER-positive breast cancer patient receiving endocrine therapy. We collected RNA expression profiling from Gene Expression Omnibus database. An ER-related signature was developed to separate patients into high-risk and low-risk groups. Patients in the low-risk group had significantly better survival than those in the high-risk group. ROC analysis indicated that this signature exhibited good diagnostic efficiency for the 1-, 3- and 5-year disease-relapse events. Moreover, multivariate Cox regression analysis demonstrated that the ER-related signature was an independent risk factor when adjusting for several clinical signatures. The prognostic value of this signature was validated in the validation sets. In addition, a nomogram was built and the calibration plots analysis indicated the good performance of this nomogram. In conclusion, combining with ER status, our results demonstrated that the ER-related prognostic signature is a promising method for predicting the prognosis of ER-positive breast cancer patients receiving endocrine therapy.

Keywords: breast cancer; estrogen receptor; nomogram; prognosis.

Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2.
Wen Min Lau, Kristy L Weber, +6 authors, Scott L Kominsky.
Int J Cancer, 2009 Jul 31; 126(4). PMID: 19642106
Estrogen receptor-related genes as an important panel of predictors for breast cancer response to neoadjuvant chemotherapy.
Yizuo Chen, Canming Chen, +10 authors, Jiong Wu.
Cancer Lett, 2011 Jan 12; 302(1). PMID: 21220187
Apoptosis-inducing and antiproliferative effect by inhibition of miR-182-5p through the regulation of CASP9 expression in human breast cancer.
M Sharifi, A Moridnia.
Cancer Gene Ther, 2017 Jan 14; 24(2). PMID: 28084318
Differential regulation of estrogen receptor alpha turnover and transactivation by Mdm2 and stress-inducing agents.
Vanessa Duong, Nathalie Boulle, +4 authors, Vincent Cavaillès.
Cancer Res, 2007 Jun 05; 67(11). PMID: 17545634
Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2.
Mingkun Chen, Rongpei Wu, +5 authors, Zike Qin.
J Exp Clin Cancer Res, 2018 Jul 18; 37(1). PMID: 30012177    Free PMC article.
Estrogen-mediated signaling is differentially affected by the expression levels of Sfrp1 in mammary epithelial cells.
Kelly J Gregory, Sallie S Schneider.
Cell Biol Int, 2015 Mar 27; 39(7). PMID: 25809273
Cyclin E expression is correlated with tumor progression and predicts a poor prognosis in patients with ovarian carcinoma.
Daniel G Rosen, Gong Yang, +4 authors, Jinsong Liu.
Cancer, 2006 Mar 29; 106(9). PMID: 16568440
Expression of MT4-MMP, EGFR, and RB in Triple-Negative Breast Cancer Strongly Sensitizes Tumors to Erlotinib and Palbociclib Combination Therapy.
Pierre Foidart, Cassandre Yip, +13 authors, Guy Jerusalem.
Clin Cancer Res, 2018 Dec 07; 25(6). PMID: 30504427
An estrogen receptor (ER)-related signature in predicting prognosis of ER-positive breast cancer following endocrine treatment.
Jianing Tang, Qiuxia Cui, +3 authors, Gaosong Wu.
J Cell Mol Med, 2019 May 28; 23(8). PMID: 31124293    Free PMC article.
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
Freddie Bray, Jacques Ferlay, +3 authors, Ahmedin Jemal.
CA Cancer J Clin, 2018 Sep 13; 68(6). PMID: 30207593
Highly Cited.
Factors predicting late recurrence for estrogen receptor-positive breast cancer.
Ivana Sestak, Mitch Dowsett, +4 authors, Jack Cuzick.
J Natl Cancer Inst, 2013 Sep 14; 105(19). PMID: 24029245    Free PMC article.
Highly Cited.
MDM2 and human malignancies: expression, clinical pathology, prognostic markers, and implications for chemotherapy.
Elizabeth Rayburn, Ruiwen Zhang, Jie He, Hui Wang.
Curr Cancer Drug Targets, 2005 Feb 22; 5(1). PMID: 15720187
SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma.
Yuen Yee Cheng, Ellie Mok, +4 authors, Glen Reid.
Dis Markers, 2018 Feb 02; 2017. PMID: 29386699    Free PMC article.
MED1 may explain the interaction between receptor tyrosine kinases and ERα66 in the complicated network of Tamoxifen resistance.
Sepideh Mansouri, Fateme Naghavi-Al-Hosseini, Leila Farahmand, Keivan Majidzadeh-A.
Eur J Pharmacol, 2017 Mar 23; 804. PMID: 28322840
Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers.
Robert Roskoski.
Pharmacol Res, 2018 Dec 01; 139. PMID: 30500458
Highly Cited. Review.
Molecular portraits of human breast tumours.
C M Perou, T Sørlie, +15 authors, D Botstein.
Nature, 2000 Aug 30; 406(6797). PMID: 10963602
Highly Cited.
Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen.
A Prat, J S Parker, +9 authors, C M Perou.
Ann Oncol, 2012 Apr 26; 23(11). PMID: 22532584    Free PMC article.
Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.
Hege O Ohnstad, Elin Borgen, +11 authors, Bjørn Naume.
Breast Cancer Res, 2017 Nov 16; 19(1). PMID: 29137653    Free PMC article.
EGFR Is Regulated by TFAP2C in Luminal Breast Cancer and Is a Target for Vandetanib.
James P De Andrade, Jung M Park, +7 authors, Ronald J Weigel.
Mol Cancer Ther, 2016 Feb 03; 15(3). PMID: 26832794    Free PMC article.
CCNE1 copy-number gain and overexpression identify ovarian clear cell carcinoma with a poor prognosis.
Ayse Ayhan, Elisabetta Kuhn, +6 authors, Tian-Li Wang.
Mod Pathol, 2016 Oct 22; 30(2). PMID: 27767100
International Web-based consultation on priorities for translational breast cancer research.
Mitch Dowsett, Aron Goldhirsch, +3 authors, Giuseppe Viale.
Breast Cancer Res, 2007 Nov 24; 9(6). PMID: 18034879    Free PMC article.
Tumor suppressor function of miR-483-3p on breast cancer via targeting of the cyclin E1 gene.
Xiaoxi Huang, Jin Lyu.
Exp Ther Med, 2018 Sep 07; 16(3). PMID: 30186493    Free PMC article.
CITED2 Modulates Breast Cancer Metastatic Ability through Effects on IKKα.
Swaathi Jayaraman, Michele Doucet, Wen Min Lau, Scott L Kominsky.
Mol Cancer Res, 2016 May 25; 14(8). PMID: 27216153    Free PMC article.
Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor-Positive Early Breast Cancer: Results of a Prospective Cohort Study.
Anne Kuijer, Marieke Straver, +8 authors, Thijs van Dalen.
J Clin Oncol, 2017 Aug 17; 35(24). PMID: 28813638
Modification of ASC1 by UFM1 is crucial for ERα transactivation and breast cancer development.
Hee Min Yoo, Sung Hwan Kang, +12 authors, Chin Ha Chung.
Mol Cell, 2014 Sep 16; 56(2). PMID: 25219498
A prognostic signature based on three-genes expression in triple-negative breast tumours with residual disease.
Joseph A Pinto, Jhajaira Araujo, +5 authors, Henry L Gomez.
NPJ Genom Med, 2016 Feb 03; 1. PMID: 29263808    Free PMC article.
HER2-Driven Breast Tumorigenesis Relies upon Interactions of the Estrogen Receptor with Coactivator MED1.
Yongguang Yang, Marissa Leonard, +6 authors, Xiaoting Zhang.
Cancer Res, 2017 Dec 01; 78(2). PMID: 29187405    Free PMC article.
Epidermal growth factor receptor and tyrosine phosphorylation of estrogen receptor.
D C Márquez, J Lee, T Lin, R J Pietras.
Endocrine, 2002 Mar 13; 16(2). PMID: 11887937
Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest.
Navdeep K Dhillon, Maria Mudryj.
Oncogene, 2002 Jul 04; 21(30). PMID: 12096339
PKA-mediated stabilization of FoxH1 negatively regulates ERalpha activity.
Jinah Yum, Hyung Min Jeong, +4 authors, Chang-Yeol Yeo.
Mol Cells, 2009 Aug 28; 28(1). PMID: 19711044
CITED2 modulates estrogen receptor transcriptional activity in breast cancer cells.
Wen Min Lau, Michele Doucet, +2 authors, Scott L Kominsky.
Biochem Biophys Res Commun, 2013 Jul 03; 437(2). PMID: 23811274    Free PMC article.
MDM2 protein expression is a negative prognostic marker in breast carcinoma.
Dmitry A Turbin, Maggie C U Cheang, +6 authors, C Blake Gilks.
Mod Pathol, 2005 Nov 01; 19(1). PMID: 16258514
A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion.
Longchuan Bai, Juanita L Merchant.
FEBS Lett, 2007 Dec 07; 581(30). PMID: 18054336    Free PMC article.
MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity.
H B Sun, Y X Zhu, +2 authors, Y C Yang.
Proc Natl Acad Sci U S A, 1998 Nov 13; 95(23). PMID: 9811838    Free PMC article.
CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer.
T van Agthoven, A M Sieuwerts, +9 authors, L C J Dorssers.
Br J Cancer, 2009 Nov 12; 101(11). PMID: 19904269    Free PMC article.
CITED2 functions as a molecular switch of cytokine-induced proliferation and quiescence.
Y-T Chou, C-H Hsieh, +9 authors, C-W Wu.
Cell Death Differ, 2012 Jul 21; 19(12). PMID: 22814619    Free PMC article.
Regulation of nuclear receptor transcriptional activity by a novel DEAD box RNA helicase (DP97).
Ramji R Rajendran, Anne C Nye, +3 authors, Benita S Katzenellenbogen.
J Biol Chem, 2002 Dec 06; 278(7). PMID: 12466272
Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells.
C Elizabeth Caldon, C Marcelo Sergio, +12 authors, Elizabeth A Musgrove.
Mol Cancer Ther, 2012 May 09; 11(7). PMID: 22564725
Estrogen receptor-dependent proteasomal degradation of the glucocorticoid receptor is coupled to an increase in mdm2 protein expression.
H Karimi Kinyamu, Trevor K Archer.
Mol Cell Biol, 2003 Aug 05; 23(16). PMID: 12897156    Free PMC article.
A nomogram combining long non-coding RNA expression profiles and clinical factors predicts survival in patients with bladder cancer.
Yifan Wang, Lutao Du, +8 authors, Chuanxin Wang.
Aging (Albany NY), 2020 Feb 13; 12(3). PMID: 32047140    Free PMC article.
Comprehensive analysis of autophagy-related prognostic genes in breast cancer.
Jianguo Lai, Bo Chen, +3 authors, Ning Liao.
J Cell Mol Med, 2020 Jul 04; 24(16). PMID: 32618109    Free PMC article.
Development and Validation of an Individualized Nomogram for Predicting Overall Survival in Patients With Typical Lung Carcinoid Tumors.
Shenghua Dong, Jun Liang, Wenxin Zhai, Zhuang Yu.
Am J Clin Oncol, 2020 Sep 06; 43(9). PMID: 32889829    Free PMC article.
An immune-related prognostic signature for predicting breast cancer recurrence.
Zelin Tian, Jianing Tang, +3 authors, Gaosong Wu.
Cancer Med, 2020 Aug 26; 9(20). PMID: 32841536    Free PMC article.
Individualized Prediction of Survival by a 10-Long Non-coding RNA-Based Prognostic Model for Patients With Breast Cancer.
Xuemei Yang, Juan Li, +9 authors, Chuanxin Wang.
Front Oncol, 2020 Nov 17; 10. PMID: 33194577    Free PMC article.
A novel nomogram for predicting liver metastasis in patients with gastrointestinal stromal tumor: a SEER-based study.
Guowei Zhou, Keshuai Xiao, +5 authors, Chaoqun Ma.
BMC Surg, 2020 Nov 27; 20(1). PMID: 33238982    Free PMC article.
Weighted gene correlation network analysis identifies microenvironment-related genes signature as prognostic candidate for Grade II/III glioma.
Yong Li, Gang Deng, +7 authors, Qianxue Chen.
Aging (Albany NY), 2020 Nov 14; 12(21). PMID: 33186124    Free PMC article.
Identification of a 9-gene prognostic signature for breast cancer.
Zelin Tian, Jianing Tang, +3 authors, Gaosong Wu.
Cancer Med, 2020 Oct 23;. PMID: 33090721    Free PMC article.
An estrogen receptor (ER)-related signature in predicting prognosis of ER-positive breast cancer following endocrine treatment.
Jianing Tang, Qiuxia Cui, +3 authors, Gaosong Wu.
J Cell Mol Med, 2019 May 28; 23(8). PMID: 31124293    Free PMC article.