Skip to main content
Top
Published in: Tumor Biology 5/2016

01-05-2016 | Original Article

High expression of FOXR2 in breast cancer correlates with poor prognosis

Authors: Haiping Song, Wenshan He, Xiaoqing Huang, Huiqiong Zhang, Tao Huang

Published in: Tumor Biology | Issue 5/2016

Login to get access

Abstract

Forkhead box protein R2 (FOXR2) is associated with human central nervous system neoplasms. However, the expression level of FOXR2 in breast cancer specimens remains largely unknown. To identify whether FOXR2 can serve as a biomarker for the diagnosis and prognosis of breast cancer, real-time PCR and immunohistochemistry (IHC) staining were utilized to detect the expression of FOXR2. The messenger RNA (mRNA) and protein levels of FOXR2 in breast cancer samples were novelty higher compared to non-tumorous breast tissues. IHC results revealed FOXR2 expression was significantly correlated to classifications tumor size (p = 0.007) and Ki-67 (p = 0.019). The patients with high expression of FOXR2 had a significantly poor prognosis compared to those of low expression (p = 0.003), especially in the patients with tumor size ≥2 cm (p = 0.006) and lymph node metastasis status (p = 0.004). Furthermore, multivariate analysis indicated that FOXR2 expression was an independent prognostic factor for breast cancer patients (p = 0.035). This study first identifies that FOXR2 may be an important molecular marker for diagnosis and prognosis of breast cancer.
Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA: Cancer J Clin. 2015;65:87–108. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA: Cancer J Clin. 2015;65:87–108.
2.
go back to reference Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015;385:977–1010.CrossRefPubMed Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015;385:977–1010.CrossRefPubMed
3.
go back to reference Ahmed M, Purushotham AD, Douek M. Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review. Lancet Oncol. 2014;15:e351–62.CrossRefPubMed Ahmed M, Purushotham AD, Douek M. Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review. Lancet Oncol. 2014;15:e351–62.CrossRefPubMed
4.
go back to reference Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, et al. Breast cancer in China. Lancet Oncol. 2014;15:e279–289.CrossRefPubMed Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, et al. Breast cancer in China. Lancet Oncol. 2014;15:e279–289.CrossRefPubMed
5.
go back to reference Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC. Early breast cancer. Lancet (London, England). 2009;373:1463–79.CrossRef Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC. Early breast cancer. Lancet (London, England). 2009;373:1463–79.CrossRef
6.
go back to reference Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the genomic health recurrence score in early breast cancer. J Clin Oncol: Off J Am Soc Clin Oncol. 2011;29:4273–8.CrossRef Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the genomic health recurrence score in early breast cancer. J Clin Oncol: Off J Am Soc Clin Oncol. 2011;29:4273–8.CrossRef
7.
go back to reference Freeman JW, McGrath P, Bondada V, Selliah N, Ownby H, Maloney T, et al. Prognostic significance of proliferation associated nucleolar antigen P120 in human breast carcinoma. Cancer Res. 1991;51:1973–8.PubMed Freeman JW, McGrath P, Bondada V, Selliah N, Ownby H, Maloney T, et al. Prognostic significance of proliferation associated nucleolar antigen P120 in human breast carcinoma. Cancer Res. 1991;51:1973–8.PubMed
8.
go back to reference Huang ZL, Lin ZR, Xiao YR, Cao X, Zhu LC, Zeng MS, et al. High expression of TACC3 in esophageal squamous cell carcinoma correlates with poor prognosis. Oncotarget. 2015;6:6850–61.CrossRefPubMedPubMedCentral Huang ZL, Lin ZR, Xiao YR, Cao X, Zhu LC, Zeng MS, et al. High expression of TACC3 in esophageal squamous cell carcinoma correlates with poor prognosis. Oncotarget. 2015;6:6850–61.CrossRefPubMedPubMedCentral
9.
go back to reference Zhou X, Zhang J, Yun H, Shi R, Wang Y, Wang W, Lagercrantz SB, Mu K: Alterations of biomarker profiles after neoadjuvant chemotherapy in breast cancer: tumor heterogeneity should be taken into consideration. Oncotarget 2015. Zhou X, Zhang J, Yun H, Shi R, Wang Y, Wang W, Lagercrantz SB, Mu K: Alterations of biomarker profiles after neoadjuvant chemotherapy in breast cancer: tumor heterogeneity should be taken into consideration. Oncotarget 2015.
10.
go back to reference Denkert C, Budczies J, von Minckwitz G, Wienert S, Loibl S, Klauschen F: Strategies for developing Ki67 as a useful biomarker in breast cancer. Breast (Edinburgh, Scotland) 2015 Denkert C, Budczies J, von Minckwitz G, Wienert S, Loibl S, Klauschen F: Strategies for developing Ki67 as a useful biomarker in breast cancer. Breast (Edinburgh, Scotland) 2015
11.
go back to reference Elkhuizen PH, van Slooten HJ, Clahsen PC, Hermans J, van de Velde CJ, van den Broek LC, et al. High local recurrence risk after breast-conserving therapy in node-negative premenopausal breast cancer patients is greatly reduced by one course of perioperative chemotherapy: a European organization for research and treatment of cancer breast cancer cooperative group study. J Clin Oncol: Off J Am Soc Clin Oncol. 2000;18:1075–83.CrossRef Elkhuizen PH, van Slooten HJ, Clahsen PC, Hermans J, van de Velde CJ, van den Broek LC, et al. High local recurrence risk after breast-conserving therapy in node-negative premenopausal breast cancer patients is greatly reduced by one course of perioperative chemotherapy: a European organization for research and treatment of cancer breast cancer cooperative group study. J Clin Oncol: Off J Am Soc Clin Oncol. 2000;18:1075–83.CrossRef
12.
go back to reference Ignatiadis M, Sotiriou C. Luminal breast cancer: from biology to treatment. Nat Rev Clin Oncol. 2013;10:494–506.CrossRefPubMed Ignatiadis M, Sotiriou C. Luminal breast cancer: from biology to treatment. Nat Rev Clin Oncol. 2013;10:494–506.CrossRefPubMed
13.
go back to reference Cui Y, Niu M, Zhang X, Zhong Z, Wang J, Pang D: High expression of valosin-containing protein predicts poor prognosis in patients with breast carcinoma. Tumour Biology: The Journal of the International Society for Oncodev Biol Med 2015. Cui Y, Niu M, Zhang X, Zhong Z, Wang J, Pang D: High expression of valosin-containing protein predicts poor prognosis in patients with breast carcinoma. Tumour Biology: The Journal of the International Society for Oncodev Biol Med 2015.
14.
go back to reference Zeidan BA, Townsend PA, Garbis SD, Copson E, Cutress RI: Clinical proteomics and breast cancer. Surgeon: J Royal Coll Surg Edinburgh Irel 2015. Zeidan BA, Townsend PA, Garbis SD, Copson E, Cutress RI: Clinical proteomics and breast cancer. Surgeon: J Royal Coll Surg Edinburgh Irel 2015.
15.
go back to reference Zardavas D, Irrthum A, Swanton C, Piccart M: Clinical management of breast cancer heterogeneity. Nat Rev Clin Oncol 2015. Zardavas D, Irrthum A, Swanton C, Piccart M: Clinical management of breast cancer heterogeneity. Nat Rev Clin Oncol 2015.
16.
go back to reference Katoh M, Katoh M. Human fox gene family (review). Int J Oncol. 2004;25:1495–500.PubMed Katoh M, Katoh M. Human fox gene family (review). Int J Oncol. 2004;25:1495–500.PubMed
17.
go back to reference Parry P, Wei Y, Evans G. Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. Genes, Chromosomes Cancer. 1994;11:79–84.CrossRefPubMed Parry P, Wei Y, Evans G. Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. Genes, Chromosomes Cancer. 1994;11:79–84.CrossRefPubMed
18.
go back to reference Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher 3rd FJ, Emanuel BS, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993;5:230–5.CrossRefPubMed Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher 3rd FJ, Emanuel BS, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993;5:230–5.CrossRefPubMed
19.
go back to reference Hillion J, Le Coniat M, Jonveaux P, Berger R, Bernard OA. AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood. 1997;90:3714–9.PubMed Hillion J, Le Coniat M, Jonveaux P, Berger R, Bernard OA. AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood. 1997;90:3714–9.PubMed
20.
go back to reference Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol: Off J Am Soc Clin Oncol. 2002;20:2672–9.CrossRef Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group. J Clin Oncol: Off J Am Soc Clin Oncol. 2002;20:2672–9.CrossRef
21.
go back to reference Katoh M, Katoh M. Identification and characterization of human FOXN6, mouse Foxn6, and rat Foxn6 genes in silico. Int J Oncol. 2004;25:219–23.PubMed Katoh M, Katoh M. Identification and characterization of human FOXN6, mouse Foxn6, and rat Foxn6 genes in silico. Int J Oncol. 2004;25:219–23.PubMed
22.
go back to reference Santo EE, Ebus ME, Koster J, Schulte JH, Lakeman A, van Sluis P, et al. Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma. Oncogene. 2012;31:1571–81.CrossRefPubMed Santo EE, Ebus ME, Koster J, Schulte JH, Lakeman A, van Sluis P, et al. Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma. Oncogene. 2012;31:1571–81.CrossRefPubMed
23.
go back to reference Nagel S, Meyer C, Kaufmann M, Drexler HG, MacLeod RA. Deregulated FOX genes in Hodgkin lymphoma. Genes, Chromosomes Cancer. 2014;53:917–33.CrossRefPubMed Nagel S, Meyer C, Kaufmann M, Drexler HG, MacLeod RA. Deregulated FOX genes in Hodgkin lymphoma. Genes, Chromosomes Cancer. 2014;53:917–33.CrossRefPubMed
24.
go back to reference Rahrmann EP, Watson AL, Keng VW, Choi K, Moriarity BS, Beckmann DA, et al. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis. Nat Genet. 2013;45:756–66.CrossRefPubMedPubMedCentral Rahrmann EP, Watson AL, Keng VW, Choi K, Moriarity BS, Beckmann DA, et al. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis. Nat Genet. 2013;45:756–66.CrossRefPubMedPubMedCentral
25.
go back to reference Koso H, Tsuhako A, Lyons E, Ward JM, Rust AG, Adams DJ, et al. Identification of FoxR2 as an oncogene in medulloblastoma. Cancer Res. 2014;74:2351–61.CrossRefPubMed Koso H, Tsuhako A, Lyons E, Ward JM, Rust AG, Adams DJ, et al. Identification of FoxR2 as an oncogene in medulloblastoma. Cancer Res. 2014;74:2351–61.CrossRefPubMed
26.
go back to reference Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.CrossRefPubMedPubMedCentral Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.CrossRefPubMedPubMedCentral
27.
go back to reference Edge SB, Byrd DR, al CCe: American Joint Committee on Cancer (AJCC) cancer staging manual, 7th edition, ed 7. Springer, 2009. Edge SB, Byrd DR, al CCe: American Joint Committee on Cancer (AJCC) cancer staging manual, 7th edition, ed 7. Springer, 2009.
28.
go back to reference Myatt SS, Lam EW. The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer. 2007;7:847–59.CrossRefPubMed Myatt SS, Lam EW. The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer. 2007;7:847–59.CrossRefPubMed
29.
go back to reference Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, et al. Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both tramp and lady transgenic mice. Cancer Res. 2006;66:1712–20.CrossRefPubMedPubMedCentral Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, et al. Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both tramp and lady transgenic mice. Cancer Res. 2006;66:1712–20.CrossRefPubMedPubMedCentral
Metadata
Title
High expression of FOXR2 in breast cancer correlates with poor prognosis
Authors
Haiping Song
Wenshan He
Xiaoqing Huang
Huiqiong Zhang
Tao Huang
Publication date
01-05-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4437-4

Other articles of this Issue 5/2016

Tumor Biology 5/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine