Cancer Chemotherapy and Pharmacology

, Volume 79, Issue 3, pp 535–543 | Cite as

Overexpression of ANLN contributed to poor prognosis of anthracycline-based chemotherapy in breast cancer patients

  • Zhan Wang
  • Juan Chen
  • Mei-Zuo Zhong
  • Juan Huang
  • Yuan-Ping Hu
  • De-Yun Feng
  • Zhi-Jiao Zhou
  • Xiao Luo
  • Zhao-Qian Liu
  • Wu-Zhong Jiang
  • Wei-Bing Zhou
Original Article



To investigate the associations of ANLN expression with prognosis of breast cancer and clinical outcome of anthracycline-based chemotherapy.


This study enrolled 308 breast cancer patients in which 264 of them received anthracycline-based chemotherapy. Immunohistochemistry was used to detect ANLN expression level of the patients. Clinical characteristics of the patients were collected, and associations of ANLN expression with prognosis were analyzed.


Our results showed that ANLN expression was associated with survival of breast cancer patients, and it was also related to clinical outcome of patients received anthracycline-based chemotherapy. Breast cancer patients with high expression of ANLN would have poor prognosis and poor clinical outcome to anthracycline-based chemotherapy.


ANLN could be an independent prognosis predictor for breast cancer, and its expression might be used to predict the anthracycline-based chemotherapy clinical outcome in breast cancer patients.


ANLN Breast cancer Anthracycline Prognosis 



This work was supported by the National Natural Science Foundation of China (81572612) and the Fundamental Research Funds for the Central Universities of Central South University (2015zzts116).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29. doi: 10.3322/caac.21254 CrossRefPubMedGoogle Scholar
  2. 2.
    Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, Chen WQ, Shao ZM, Goss PE (2014) Breast cancer in China. Lancet Oncol 15(7):e279–e289. doi: 10.1016/S1470-2045(13)70567-9 CrossRefPubMedGoogle Scholar
  3. 3.
    Winchester DP (2011) Post-treatment surveillance of breast cancer patients in an organized, multidisciplinary setting. J Surg Oncol 103(4):358–361. doi: 10.1002/jso.21713 CrossRefPubMedGoogle Scholar
  4. 4.
    von Minckwitz G, Raab G, Caputo A, Schutte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23(12):2676–2685. doi: 10.1200/JCO.2005.05.078 CrossRefGoogle Scholar
  5. 5.
    Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N (2005) Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 23(16):3686–3696. doi: 10.1200/JCO.2005.10.517 CrossRefPubMedGoogle Scholar
  6. 6.
    Hintzpeter J, Seliger JM, Hofman J, Martin HJ, Wsol V, Maser E (2016) Inhibition of human anthracycline reductases by emodin—a possible remedy for anthracycline resistance. Toxicol Appl Pharmacol 293:21–29. doi: 10.1016/j.taap.2016.01.003 CrossRefPubMedGoogle Scholar
  7. 7.
    Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF (1984) Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science 226(4673):466–468CrossRefPubMedGoogle Scholar
  8. 8.
    Swift LP, Rephaeli A, Nudelman A, Phillips DR, Cutts SM (2006) Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell death. Cancer Res 66(9):4863–4871. doi: 10.1158/0008-5472.CAN-05-3410 CrossRefPubMedGoogle Scholar
  9. 9.
    Cutts SM, Rephaeli A, Nudelman A, Ugarenko M, Phillips DR (2015) Potential therapeutic advantages of doxorubicin when activated by formaldehyde to function as a dna adduct-forming agent. Curr Top Med Chem 15(14):1409–1422CrossRefPubMedGoogle Scholar
  10. 10.
    Nielsen D, Maare C, Skovsgaard T (1996) Cellular resistance to anthracyclines. General Pharmacol 27(2):251–255CrossRefGoogle Scholar
  11. 11.
    Marquette C, Nabell L (2012) Chemotherapy-resistant metastatic breast cancer. Curr Treat Options Oncol 13(2):263–275. doi: 10.1007/s11864-012-0184-6 CrossRefPubMedGoogle Scholar
  12. 12.
    Bilardi RA, Kimura KI, Phillips DR, Cutts SM (2012) Processing of anthracycline-DNA adducts via DNA replication and interstrand crosslink repair pathways. Biochem Pharmacol 83(9):1241–1250. doi: 10.1016/j.bcp.2012.01.029 CrossRefPubMedGoogle Scholar
  13. 13.
    Field CM, Alberts BM (1995) Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. J Cell Biol 131(1):165–178CrossRefPubMedGoogle Scholar
  14. 14.
    Oegema K, Savoian MS, Mitchison TJ, Field CM (2000) Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol 150(3):539–552CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhou W, Wang Z, Shen N, Pi W, Jiang W, Huang J, Hu Y, Li X, Sun L (2015) Knockdown of ANLN by lentivirus inhibits cell growth and migration in human breast cancer. Mol Cell Biochem 398(1–2):11–19. doi: 10.1007/s11010-014-2200-6 CrossRefPubMedGoogle Scholar
  16. 16.
    Wang G, Shen W, Cui L, Chen W, Hu X, Fu J (2016) Overexpression of Anillin (ANLN) is correlated with colorectal cancer progression and poor prognosis. Cancer Biomark 16 (3):459–465. doi: 10.3233/CBM-160585 CrossRefPubMedGoogle Scholar
  17. 17.
    Pandi NS, Manimuthu M, Harunipriya P, Murugesan M, Asha GV, Rajendran S (2014) In silico analysis of expression pattern of a Wnt/beta-catenin responsive gene ANLN in gastric cancer. Gene 545(1):23–29. doi: 10.1016/j.gene.2014.05.013 CrossRefPubMedGoogle Scholar
  18. 18.
    Suzuki C, Daigo Y, Ishikawa N, Kato T, Hayama S, Ito T, Tsuchiya E, Nakamura Y (2005) ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway. Cancer Res 65(24):11314–11325. doi: 10.1158/0008-5472.CAN-05-1507 CrossRefPubMedGoogle Scholar
  19. 19.
    Olakowski M, Tyszkiewicz T, Jarzab M, Krol R, Oczko-Wojciechowska M, Kowalska M, Kowal M, Gala GM, Kajor M, Lange D, Chmielik E, Gubala E, Lampe P, Jarzab B (2009) NBL1 and anillin (ANLN) genes over-expression in pancreatic carcinoma. Folia histochemica et cytobiologica/Polish Academy of Sciences, Polish Histochemical and Cytochemical. Society 47(2):249–255. doi: 10.2478/v10042-009-0031-1 Google Scholar
  20. 20.
    PC OL, Penny SA, Dolan RT, Kelly CM, Madden SF, Rexhepaj E, Brennan DJ, McCann AH, Ponten F, Uhlen M, Zagozdzon R, Duffy MJ, Kell MR, Jirstrom K, Gallagher WM (2013) Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer. BMC Cancer 13:175. doi: 10.1186/1471-2407-13-175 CrossRefGoogle Scholar
  21. 21.
    Piekny AJ, Maddox AS (2010) The myriad roles of Anillin during cytokinesis. Semin Cell Dev Biol 21(9):881–891. doi: 10.1016/j.semcdb.2010.08.002 CrossRefPubMedGoogle Scholar
  22. 22.
    Zhao WM, Fang G (2005) Anillin is a substrate of anaphase-promoting complex/cyclosome (APC/C) that controls spatial contractility of myosin during late cytokinesis. J Biol Chem 280(39):33516–33524. doi: 10.1074/jbc.M504657200 CrossRefPubMedGoogle Scholar
  23. 23.
    Klippel A, Escobedo MA, Wachowicz MS, Apell G, Brown TW, Giedlin MA, Kavanaugh WM, Williams LT (1998) Activation of phosphatidylinositol 3-kinase is sufficient for cell cycle entry and promotes cellular changes characteristic of oncogenic transformation. Mol Cell Biol 18(10):5699–5711CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chun KH, Kosmeder JW 2nd, Sun S, Pezzuto JM, Lotan R, Hong WK, Lee HY (2003) Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells. J Natl Cancer Inst 95(4):291–302CrossRefPubMedGoogle Scholar
  25. 25.
    Bartek J, Lukas J (2011) DNA repair: cyclin D1 multitasks. Nature 474(7350):171–172. doi: 10.1038/474171a CrossRefPubMedGoogle Scholar
  26. 26.
    Graeser M, McCarthy A, Lord CJ, Savage K, Hills M, Salter J, Orr N, Parton M, Smith IE, Reis-Filho JS, Dowsett M, Ashworth A, Turner NC (2010) A marker of homologous recombination predicts pathologic complete response to neoadjuvant chemotherapy in primary breast cancer. Clin Cancer Res 16(24):6159–6168. doi: 10.1158/1078-0432.CCR-10-1027 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30. doi: 10.3322/caac.21332 CrossRefPubMedGoogle Scholar
  28. 28.
    Ross JS, Linette GP, Stec J, Clark E, Ayers M, Leschly N, Symmans WF, Hortobagyi GN, Pusztai L (2003) Breast cancer biomarkers and molecular medicine. Expert Rev Mol Diagn 3(5):573–585. doi: 10.1586/14737159.3.5.573 CrossRefPubMedGoogle Scholar
  29. 29.
    Ross JS, Linette GP, Stec J, Clark E, Ayers M, Leschly N, Symmans WF, Hortobagyi GN, Pusztai L (2004) Breast cancer biomarkers and molecular medicine: part II. Expert Rev Mol Diagn 4(2):169–188. doi: 10.1586/14737159.4.2.169 CrossRefPubMedGoogle Scholar
  30. 30.
    Hall PA, Todd CB, Hyland PL, McDade SS, Grabsch H, Dattani M, Hillan KJ, Russell SE (2005) The septin-binding protein anillin is overexpressed in diverse human tumors. Clini Cancer Res 11(19):6780–6786. doi: 10.1158/1078-0432.CCR-05-0997 CrossRefGoogle Scholar
  31. 31.
    Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, Citron ML, Campone M, Xu N, Smitt M, Gianni L (2015) Feasibility and cardiac safety of trastuzumab emtansine after anthracycline-based chemotherapy as (neo)adjuvant therapy for human epidermal growth factor receptor 2-positive early-stage breast cancer. J Clin Oncol 33(10):1136–1142. doi: 10.1200/JCO.2014.58.7782 CrossRefPubMedGoogle Scholar
  32. 32.
    Ghanbari S, Ayatollahi SM, Zare N (2015) Comparing role of two chemotherapy regimens, cmf and anthracycline-based, on breast cancer survival in the eastern mediterranean region and Asia by multivariate mixed effects models: a meta-analysis. Asian Pac J Cancer Prev: APJCP 16(14):5655–5661CrossRefPubMedGoogle Scholar
  33. 33.
    Bang SM, Heo DS, Lee KH, Byun JH, Chang HM, Noh DY, Choe KJ, Bang YJ, Kim SR, Kim NK (2000) Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma. Cancer 89(12):2521–2526CrossRefPubMedGoogle Scholar
  34. 34.
    Jones S, Holmes FA, O’Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA (2009) Docetaxel With cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US oncology research trial 9735. J Clin Oncol 27(8):1177–1183. doi: 10.1200/JCO.2008.18.4028 CrossRefPubMedGoogle Scholar
  35. 35.
    Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M et al (1994) c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330(18):1260–1266. doi: 10.1056/NEJM199405053301802 CrossRefPubMedGoogle Scholar
  36. 36.
    Mehta RS, Schubbert T (2008) Re: HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 100(9):680. doi: 10.1093/jnci/djn107 (author reply 680–681)CrossRefPubMedGoogle Scholar
  37. 37.
    Spencer DM, Bilardi RA, Koch TH, Post GC, Nafie JW, Kimura K, Cutts SM, Phillips DR (2008) DNA repair in response to anthracycline-DNA adducts: a role for both homologous recombination and nucleotide excision repair. Mutat Res 638(1–2):110–121. doi: 10.1016/j.mrfmmm.2007.09.005 CrossRefPubMedGoogle Scholar
  38. 38.
    Raaphorst GP, Leblanc M, Li LF (2005) A comparison of response to cisplatin, radiation and combined treatment for cells deficient in recombination repair pathways. Anticancer Res 25 (1A):53–58PubMedGoogle Scholar
  39. 39.
    Horton JK, Wilson SH (2007) Hypersensitivity phenotypes associated with genetic and synthetic inhibitor-induced base excision repair deficiency. DNA Repair 6(4):530–543. doi: 10.1016/j.dnarep.2006.10.016 CrossRefPubMedGoogle Scholar
  40. 40.
    Gillett C, Smith P, Gregory W, Richards M, Millis R, Peters G, Barnes D (1996) Cyclin D1 and prognosis in human breast cancer. Int J Cancer 69(2):92–99. doi: 10.1002/(SICI)1097-0215(19960422)69:2<92::AID-IJC4>3.0.CO;2-Q CrossRefPubMedGoogle Scholar
  41. 41.
    Zhou Q, Fukushima P, DeGraff W, Mitchell JB, Stetler Stevenson M, Ashkenazi A, Steeg PS (2000) Radiation and the Apo2L/TRAIL apoptotic pathway preferentially inhibit the colonization of premalignant human breast cells overexpressing cyclin D1. Cancer Res 60(10):2611–2615PubMedGoogle Scholar
  42. 42.
    Li Z, Jiao X, Wang C, Shirley LA, Elsaleh H, Dahl O, Wang M, Soutoglou E, Knudsen ES, Pestell RG (2010) Alternative cyclin D1 splice forms differentially regulate the DNA damage response. Cancer Res 70(21):8802–8811. doi: 10.1158/0008-5472.CAN-10-0312 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Zhan Wang
    • 1
  • Juan Chen
    • 2
    • 3
  • Mei-Zuo Zhong
    • 1
  • Juan Huang
    • 4
  • Yuan-Ping Hu
    • 4
  • De-Yun Feng
    • 5
  • Zhi-Jiao Zhou
    • 6
  • Xiao Luo
    • 7
  • Zhao-Qian Liu
    • 2
    • 3
  • Wu-Zhong Jiang
    • 1
  • Wei-Bing Zhou
    • 1
  1. 1.Department of OncologyXiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
  2. 2.Department of Clinical PharmacologyXiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
  3. 3.Hunan Key Laboratory of PharmacogeneticsInstitute of Clinical Pharmacology, Central South UniversityChangshaPeople’s Republic of China
  4. 4.Hunan Province Clinic Meditech Research Center for Breast CancerChangshaPeople’s Republic of China
  5. 5.Department of PathologyXiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
  6. 6.Department of PathologyThe third Xiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
  7. 7.Department of PainThe third Xiangya Hospital, Central South UniversityChangshaPeople’s Republic of China

Personalised recommendations