nach oben

Erschienen in:

02.04.2019 | Preclinical study

Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer

verfasst von: Sasagu Kurozumi, Chitra Joseph, Sara Raafat, Sultan Sonbul, Yousif Kariri, Sami Alsaeed, Marian Pigera, Mansour Alsaleem, Christopher C. Nolan, Simon J. Johnston, Mohammed A. Aleskandarany, Angela Ogden, Takaaki Fujii, Ken Shirabe, Stewart G. Martin, Ibraheem Alshankyty, Nigel P. Mongan, Ian O. Ellis, Andrew R. Green, Emad A. Rakha

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Androgen receptor (AR) and AR signaling pathways are thought to play a role in breast cancer (BC) and are potentially related to treatment responses and outcomes. Ankyrin 3 (ANK3) is associated with AR stability in cancer cells. In the present study, we investigated the clinicopathological utility of ANK3 expression with emphasis on AR and its associated signalling pathway at transcriptomic and proteomic phases.

Patients and methods

The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1980) and The Cancer Genome Atlas (TCGA) dataset (n = 1039) were used to assess the expression and significance of ANK3 mRNA and other AR signalling pathway-associated gene signature. Using immunohistochemistry, ANK3 protein expression was evaluated in large (n = 982) cohort of early-stage BC with long-term follow-up and compared with clinicopathological characteristics and its prognostic value in the whole cohort and the subgroups stratified by AR protein expression.

Results

An AR-related gene signature was developed, comprising 20 genes, which included ANK3. This AR-related gene signature was significantly associated with AR mRNA expression, oestrogen receptor, human epidermal growth factor receptor 2 (HER2) status and the patients’ outcomes. In tumours with high AR protein expression (n = 614), high ANK3 protein expression was significantly associated with progesterone receptor positivity and it was independently associated with the good outcomes (p = 0.025).

Conclusions

This study indicates that ANK3 is related to AR signalling pathway and is associated with BC prognosis.

Nur mit Berechtigung zugänglich

Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel Members (2015) Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 26:1533–1546CrossRefPubMedPubMedCentral

Curigliano G, Burstein HJ, Winer PE, Gnant M, Dubsky P, Loibl S, Colleoni M, Regan MM, Piccart-Gebhart M, Senn HJ, Thürlimann B, St. Gallen International expert consensus on the primary therapy of early breast cancer 2017 (2017) De-escalating and escalating treatments for early-stage breast cancer: the St Gallen International Expert Consensus Conference on the primary therapy of early breast cancer 2017. Ann Oncol 28:1700–1712CrossRefPubMedPubMedCentral

Kurozumi S, Matsumoto H, Hayashi Y, Tozuka K, Inoue K, Horiguchi J, Takeyoshi I, Oyama T, Kurosumi M (2017) Power of PgR expression as a prognostic factor for ER-positive/HER2-negative breast cancer patients at intermediate risk classified by the Ki67 labelling index. BMC Cancer 17:354CrossRefPubMedPubMedCentral

Hayashi S, Yamaguchi Y (2008) Estrogen signalling pathway and hormonal therapy. Breast Cancer 15:256–261CrossRefPubMed

Iacopetta D, Rechoum Y, Fuqua SA (2012) The role of androgen receptor in breast cancer. Drug Discov Today Dis Mech 9:e19–e27CrossRefPubMedPubMedCentral

Rampurwala M, Wisinski KB, O’Regan R (2016) Role of the androgen receptor in triple-negative breast cancer. Clin Adv Hematol Oncol 14:186–193PubMedPubMedCentral

Aleskandarany MA, Abduljabbar R, Ashankyty I, Elmouna A, Jerjees D, Ali S, Buluwela L, Diez-Rodriguez M, Caldas C, Green AR, Ellis IO, Rakha EA (2016) Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis. Breast Cancer Res Treat 159:215–227CrossRefPubMed

Vera-Badillo FE, Templeton AJ, de Gouveia P, Diaz-Padilla I, Bedard PL, Al-Mubarak M, Seruga B, Tannock IF, Ocana A, Amir E (2014) Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst 106:319CrossRef

He L, Du Z, Xiong X, Ma H, Zhu Z, Gao H, Cao J, Li T, Li H, Yang K, Chen G, Richer JK, Gu H (2017) Targeting androgen receptor in treating HER2 positive breast cancer. Sci Rep 7:14584CrossRefPubMedPubMedCentral

10.

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767CrossRefPubMedPubMedCentral

11.

Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, Valero V, Lehmann BD, Pietenpol JA, Hortobagyi GN, Symmans WF, Ueno NT (2013) Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 19:5533–5540CrossRefPubMed

12.

Fujii R, Hanamura T, Suzuki T, Gohno T, Shibahara Y, Niwa T, Yamaguchi Y, Ohnuki K, Kakugawa Y, Hirakawa H, Ishida T, Sasano H, Ohuchi N, Hayashi S (2014) Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. J Steroid Biochem Mol Biol 144:513–522CrossRefPubMed

13.

Lambert S, Bennett V (1993) From anemia to cerebellar dysfunction. A review of the ankyrin gene family. Eur J Biochem 211:1–6CrossRefPubMed

14.

Bennett V (1992) Ankyrins. Adaptors between diverse plasma membrane proteins and the cytoplasm. J Biol Chem 267:8703–8706PubMed

15.

De Matteis MA, Morrow JS (1998) The role of ankyrin and spectrin in membrane transport and domain formation. Curr Opin Cell Biol 10:542–549CrossRefPubMed

16.

Wang T, Abou-Ouf H, Hegazy SA, Alshalalfa M, Stoletov K, Lewis J, Donnelly B, Bismar TA (2016) Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients. J Mol Med (Berl) 94:1411–1422CrossRef

17.

Ramos-Montoya A, Lamb AD, Russell R, Carroll T, Jurmeister S, Galeano-Dalmau N, Massie CE, Boren J, Bon H, Theodorou V, Vias M, Shaw GL, Sharma NL, Ross-Adams H, Scott HE, Vowler SL, Howat WJ, Warren AY, Wooster RF, Mills IG, Neal DE (2014) HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network. EMBO Mol Med 6:651–661CrossRefPubMedPubMedCentral

18.

Pietri E, Conteduca V, Andreis D, Massa I, Melegari E, Sarti S, Cecconetto L, Schirone A, Bravaccini S, Serra P, Fedeli A, Maltoni R, Amadori D, De Giorgi U, Rocca A (2016) Androgen receptor signaling pathways as a target for breast cancer treatment. Endocr Relat Cancer 23:R485–R498CrossRefPubMed

19.

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock GB (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29CrossRefPubMedPubMedCentral

20.

The Gene Ontology Consortium (2017) Expansion of the gene ontology knowledgebase and resources. Nucleic Acids Res 45:D331–D338CrossRef

21.

Rhee SY, Wood V, Dolinski K, Draghici S (2008) Use and misuse of the gene ontology annotations. Nat Rev Genet 9:509–515CrossRefPubMed

22.

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550CrossRefPubMedPubMedCentral

23.

Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273CrossRefPubMed

24.

Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Gräf S (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486:346–352CrossRefPubMedPubMedCentral

25.

Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, Pugh M, Jones L, Russell R, Sammut SJ, Tsui DW (2016) The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun 10:11479CrossRef

26.

Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70CrossRef

27.

Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404CrossRefPubMed

28.

Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863–14868CrossRefPubMedPubMedCentral

29.

De Hoon MJL, Imoto S, Nolan J, Miyano S (2004) Open source clustering software. Bioinformatics 20:1453–1454CrossRefPubMed

30.

Rakha EA, Agarwal D, Green AR, Ashankyty I, Ellis IO, Ball G, Alaskandarany MA (2017) Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer. Histopathology 70:622–631CrossRefPubMed

31.

Rakha EA, Elsheikh SE, Aleskandarany MA, Habashi HO, Green AR, Powe DG, El-Sayed ME, Benhasouna A, Brunet JS, Akslen LA, Evans AJ (2009) Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes. Clin Cancer Res 15:2302–2310CrossRefPubMed

32.

Green AR, Powe DG, Rakha EA, Soria D, Lemetre C, Nolan CC, Barros FF, Macmillan RD, Garibaldi JM, Ball GR, Ellis IO (2013) Identification of key clinical phenotypes of breast cancer using a reduced panel of protein biomarkers. Br J Cancer 109:1886–1894CrossRefPubMedPubMedCentral

33.

Rakha EA, Soria D, Green AR, Lemetre C, Powe DG, Nolan CC, Garibaldi JM, Ball G, Ellis IO (2014) Nottingham Prognostic Index Plus (NPI +): a modern clinical decision making tool in breast cancer. Br J Cancer 110:1688–1697CrossRefPubMedPubMedCentral

34.

Habashy HO, Powe DG, Rakha EA, Ball G, Paish C, Gee J, Nicholson RI, Ellis IO (2008) Forkhead-box A1 (FOXA1) expression in breast cancer and its prognostic significance. Eur J Cancer 44:1541–1551CrossRefPubMed

35.

Habashy HO, Powe DG, Glaab E, Ball G, Spiteri I, Krasnogor N, Garibaldi JM, Rakha EA, Green AR, Caldas C, Ellis IO (2011) RERG (Ras-like, oestrogen-regulated, growth-inhibitor) expression in breast cancer: a marker of ER-positive luminal-like subtype. Breast Cancer Res Treat 128:315–326CrossRefPubMed

36.

Aleskandarany MA, Rakha EA, Ahmed MA, Powe DG, Ellis IO, Green AR (2011) Clinicopathologic and molecular significance of phosphor-Akt expression in early invasive breast cancer. Breast Cancer Res Treat 127:407–416CrossRefPubMed

37.

Aleskandarany MA, Rakha EA, Ahmed MA, Powe DG, Paish EC, Macmillan RD, Ellis IO, Green AR (2010) PIK3CA expression in invasive breast cancer: a biomarker of poor prognosis. Breast Cancer Res Treat 122:45–53CrossRefPubMed

38.

Joseph C, Macnamara O, Craze M, Russell R, Provenzano E, Nolan CC, Diez-Rodriguez M, Sonbul SN, Aleskandarany MA, Green AR, Rakha EA (2018) Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER + luminal subtypes. Br J Cancer 118:1142–1151CrossRefPubMedPubMedCentral

39.

Kurozumi S, Joseph C, Sonbul S, Aleskandarany MA, Pigera M, Alsaleem M, Alsaeed S, Kariri Y, Nolan CC, Diez-Rodriguez M, Johnston S, Mongan NP, Fujii T, Shirabe K, Martin SG, Ellis IO, Green AR, Rakha EA (2018) Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer. Breast Cancer Res Treat 25:236. https://doi.org/10.1007/s10549-018-4891-y CrossRef

40.

Kurozumi S, Joseph C, Sonbul S, Gorringe KL, Pigera M, Aleskandarany MA, Diez-Rodriguez M, Nolan CC, Fujii T, Shirabe K, Kuwano H, Storr S, Martin SG, Ellis IO, Green AR, Rakha EA (2018) Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis. Breast Cancer Res Treat 170:525–533CrossRefPubMed

41.

McCarty KS Jr, Miller LS, Cox EB, Konrath J, McCarty KS Sr (1985) Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 109:716–721PubMed

42.

Detre S, Saclani Jotti G, Dowsett MA (1995) “Quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48:876–878CrossRefPubMedPubMedCentral

43.

Dimitrakakis C, Bondy C (2009) Androgens and the breast. Breast Cancer Res 11:212CrossRefPubMedPubMedCentral

44.

Garay JP, Karakas B, Abukhdeir AM, Cosgrove DP, Gustin JP, Higgins MJ, Konishi H, Konishi Y, Lauring J, Mohseni M, Wang GM, Jelovac D, Weeraratna A, Sherman Baust CA, Morin PJ, Toubaji A, Meeker A, De Marzo AM, Lewis G, Subhawong A, Argani P, Park BH (2012) The growth response to androgen receptor signaling in ERα-negative human breast cells is dependent on p21 and mediated by MAPK activation. Breast Cancer Res 14:R27CrossRefPubMedPubMedCentral

45.

Chia KM, Liu J, Francis GD, Naderi A (2011) A feedback loop between androgen receptor and ERK signaling in estrogen receptor-negative breast cancer. Neoplasia 13:154–166CrossRefPubMedPubMedCentral

46.

Glinsky GV, Berezovska O, Glinskii AB (2005) Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 115:1503–1521CrossRefPubMedPubMedCentral

47.

Gröger CJ, Grubinger M, Waldhör T, Vierlinger K, Mikulits W (2012) Meta-analysis of gene expression signatures defining the epithelial to mesenchymal transition during cancer progression. PLoS ONE 7:e51136CrossRefPubMedPubMedCentral

48.

Bismar TA, Alshalalfa M, Petersen LF, Teng LH, Gerke T, Bakkar A, Al-Mami A, Liu S, Dolph M, Mucci LA, Alhajj R (2014) Interrogation of ERG gene rearrangements in prostate cancer identifies a prognostic 10-gene signature with relevant implication to patients’ clinical outcome. BJU Int 113:309–319CrossRefPubMed

49.

Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM (2010) An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer Cell 17:443–454CrossRefPubMedPubMedCentral

50.

Shah AV, Birdsey GM, Randi AM (2016) Regulation of endothelial homeostasis, vascular development and angiogenesis by the transcription factor ERG. Vascul Pharmacol 86:3–13CrossRefPubMedPubMedCentral

51.

Polson ES, Lewis JL, Celik H, Mann VM, Stower MJ, Simms MS, Rodrigues G, Collins AT, Maitland NJ (2013) Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells. Nat Commun 4:1623CrossRefPubMed

52.

Vranic S, Feldman R, Gatalica Z (2017) Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers. Bosn J Basic Med Sci 17:9–11PubMedPubMedCentral

53.

Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA, Translational Breast Cancer Research Consortium (TBCRC 011) (2019) Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res 19:5505–5512CrossRef

54.

O’Shaughnessy J, Campone M, Brain E, Neven P, Hayes D, Bondarenko I, Griffin TW, Martin J, De Porre P, Kheoh T, Yu MK, Peng W, Johnston S (2016) Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Ann Oncol 27:106–113CrossRefPubMed

55.

Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O’Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J (2018) Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol 36:884–890CrossRefPubMedPubMedCentral

Titel: Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer
verfasst von: Sasagu Kurozumi
Chitra Joseph
Sara Raafat
Sultan Sonbul
Yousif Kariri
Sami Alsaeed
Marian Pigera
Mansour Alsaleem
Christopher C. Nolan
Simon J. Johnston
Mohammed A. Aleskandarany
Angela Ogden
Takaaki Fujii
Ken Shirabe
Stewart G. Martin
Ibraheem Alshankyty
Nigel P. Mongan
Ian O. Ellis
Andrew R. Green
Emad A. Rakha
Publikationsdatum: 02.04.2019
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05216-w

Neu im Fachgebiet Onkologie

20.04.2024 | EAU 2024 | Kongressbericht | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer

Abstract

Purpose

Patients and methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Blasenkarzinom – Biomarker statt Zytologie?

Prostatakarzinom: EU initiiert neues Screeningkonzept

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Patients and methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2019

Temporal trends and regional variation in the utilization of low-value breast cancer care: has the Choosing Wisely campaign made a difference?

Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women

Pathologic discordance to clinical management decisions suggests overtreatment in pediatric benign breast disease

The association between mammographic density and breast cancer risk in Western Australian Aboriginal women

Propagation of functional estrogen receptor positive normal human breast cells in 3D cultures

Lapatinib activity in metastatic human epidermal growth factor receptor 2-positive breast cancers that received prior therapy with trastuzumab, pertuzumab, and/or ado-trastuzumab emtansine (T-DM1)

Neu im Fachgebiet Onkologie

Blasenkarzinom – Biomarker statt Zytologie?

Prostatakarzinom: EU initiiert neues Screeningkonzept

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Update Onkologie