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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

NUP98 – a novel predictor of response to anthracycline-based chemotherapy in triple negative breast cancer

Authors: Paul B. Mullan, Victoria Bingham, Paula Haddock, Gareth W. Irwin, Elaine Kay, Stephen McQuaid, Niamh E. Buckley

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Triple Negative breast cancer (TNBC) is a poor outcome subgroup of breast cancer defined based on the absence of expression of ERα and PR and HER2 amplification. These hard to treat cancers lack targeted treatment options and are therefore treated with a standard of care (SoC) generic cocktail of DNA damaging chemotherapy, with a wide range of clinical responses. While a subset of TNBC patients respond very well to this treatment, others receive no clinical benefit and die from their disease within a short time period. We currently lack biomarkers to prospectively identify patients likely to relapse and we lack alternate treatment options.

Methods

NUP98 protein expression was investigated in patient samples using two independent tissue microarrays (TMAs), as well as a normal breast TMA. Correlation with pathological response to various chemotherapy regimens was investigated.

Results

We have shown that high NUP98 is significantly associated with poor outcome in TNBC patient samples both by gene expression and IHC-based protein analysis. While trends linking NUP98 expression with poorer outcomes were observed in breast cancer overall (and more specifically in the LuminalB Her2- subgroup), significant correlations were observed in TNBC. This appeared to be specific to anthracycline based regimens as the association between NUP98 and response was not observed in patients treated with taxane-based chemotherapy.

Conclusions

We have identified a novel biomarker, NUP98, that can predict response to anthracycline based chemotherapy in TNBC. The ability to prospectively identify patients who are less likely to respond to SoC chemotherapy is a vital step in improving the overall survival of these patients.
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Literature
1.
go back to reference Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.CrossRef Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.CrossRef
2.
go back to reference Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, 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.CrossRef Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, 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.CrossRef
3.
go back to reference Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13(11):674–90.CrossRef Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13(11):674–90.CrossRef
4.
go back to reference Buckley NE, Haddock P, Simoes RD, Parkes E, Irwin G, Emmert-Streib F, et al. A BRCA1 deficient, NF kappa B driven immune signal predicts good outcome in triple negative breast cancer. Oncotarget. 2016;7(15):19884–96.CrossRef Buckley NE, Haddock P, Simoes RD, Parkes E, Irwin G, Emmert-Streib F, et al. A BRCA1 deficient, NF kappa B driven immune signal predicts good outcome in triple negative breast cancer. Oncotarget. 2016;7(15):19884–96.CrossRef
5.
go back to reference Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33(1):1–22.CrossRef Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33(1):1–22.CrossRef
6.
go back to reference Boyle DP, McArt DG, Irwin G, Wilhelm-Benartzi CS, Lioe TF, Sebastian E, et al. The prognostic significance of the aberrant extremes of p53 immunophenotypes in breast cancer. Histopathology. 2014;65(3):340–52.CrossRef Boyle DP, McArt DG, Irwin G, Wilhelm-Benartzi CS, Lioe TF, Sebastian E, et al. The prognostic significance of the aberrant extremes of p53 immunophenotypes in breast cancer. Histopathology. 2014;65(3):340–52.CrossRef
7.
go back to reference Orr K, Buckley NE, Haddock P, James C, Parent JL, McQuaid S, et al. Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs). Oncotarget. 2016;7(34):55458–72.CrossRef Orr K, Buckley NE, Haddock P, James C, Parent JL, McQuaid S, et al. Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs). Oncotarget. 2016;7(34):55458–72.CrossRef
8.
go back to reference Tripathi A, King C, de la Morenas A, Perry VK, Burke B, Antoine GA, et al. Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients. Int J Cancer. 2008;122(7):1557–66.CrossRef Tripathi A, King C, de la Morenas A, Perry VK, Burke B, Antoine GA, et al. Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients. Int J Cancer. 2008;122(7):1557–66.CrossRef
9.
go back to reference McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005;93(4):387–91.CrossRef McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005;93(4):387–91.CrossRef
10.
go back to reference Iwamoto M, Asakawa H, Hiraoka Y, Haraguchi T. Nucleoporin Nup98: a gatekeeper in the eukaryotic kingdoms. Genes Cells. 2010;15(7):661–9.CrossRef Iwamoto M, Asakawa H, Hiraoka Y, Haraguchi T. Nucleoporin Nup98: a gatekeeper in the eukaryotic kingdoms. Genes Cells. 2010;15(7):661–9.CrossRef
11.
go back to reference Fontoura BM, Blobel G, Matunis MJ. A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96. J Cell Biol. 1999;144(6):1097–112.CrossRef Fontoura BM, Blobel G, Matunis MJ. A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96. J Cell Biol. 1999;144(6):1097–112.CrossRef
12.
go back to reference Vasconcelos I, Hussainzada A, Berger S, Fietze E, Linke J, Siedentopf F, et al. The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival. Breast. 2016;29:181–5.CrossRef Vasconcelos I, Hussainzada A, Berger S, Fietze E, Linke J, Siedentopf F, et al. The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival. Breast. 2016;29:181–5.CrossRef
13.
go back to reference Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439–46.CrossRef Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439–46.CrossRef
14.
go back to reference Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13(11):3207–14.CrossRef Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13(11):3207–14.CrossRef
15.
go back to reference Bonnefoi H, Potti A, Delorenzi M, Mauriac L, Campone M, Tubiana-Hulin M, et al. Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncol. 2007;8(12):1071–8.CrossRef Bonnefoi H, Potti A, Delorenzi M, Mauriac L, Campone M, Tubiana-Hulin M, et al. Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncol. 2007;8(12):1071–8.CrossRef
16.
go back to reference Iwamoto T, Bianchini G, Booser D, Qi Y, Coutant C, Shiang CY, et al. Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer. J Natl Cancer Inst. 2011;103(3):264–72.CrossRef Iwamoto T, Bianchini G, Booser D, Qi Y, Coutant C, Shiang CY, et al. Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer. J Natl Cancer Inst. 2011;103(3):264–72.CrossRef
17.
go back to reference Tabchy A, Valero V, Vidaurre T, Lluch A, Gomez H, Martin M, et al. Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer. Clin Cancer Res. 2010;16(21):5351–61.CrossRef Tabchy A, Valero V, Vidaurre T, Lluch A, Gomez H, Martin M, et al. Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer. Clin Cancer Res. 2010;16(21):5351–61.CrossRef
18.
go back to reference Cautain B, Hill R, de Pedro N, Link W. Components and regulation of nuclear transport processes. FEBS J. 2015;282(3):445–62.CrossRef Cautain B, Hill R, de Pedro N, Link W. Components and regulation of nuclear transport processes. FEBS J. 2015;282(3):445–62.CrossRef
19.
go back to reference Kim YH, Han ME, Oh SO. The molecular mechanism for nuclear transport and its application. Anat Cell Biol. 2017;50(2):77–85.CrossRef Kim YH, Han ME, Oh SO. The molecular mechanism for nuclear transport and its application. Anat Cell Biol. 2017;50(2):77–85.CrossRef
20.
go back to reference Griffis ER, Xu S, Powers MA. Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes. Mol Biol Cell. 2003;14(2):600–10.CrossRef Griffis ER, Xu S, Powers MA. Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes. Mol Biol Cell. 2003;14(2):600–10.CrossRef
21.
go back to reference Pritchard CE, Fornerod M, Kasper LH, van Deursen JM. RAE1 is a shuttling mRNA export factor that binds to a GLEBS-like NUP98 motif at the nuclear pore complex through multiple domains. J Cell Biol. 1999;145(2):237–54.CrossRef Pritchard CE, Fornerod M, Kasper LH, van Deursen JM. RAE1 is a shuttling mRNA export factor that binds to a GLEBS-like NUP98 motif at the nuclear pore complex through multiple domains. J Cell Biol. 1999;145(2):237–54.CrossRef
22.
go back to reference Kalverda B, Pickersgill H, Shloma VV, Fornerod M. Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm. Cell. 2010;140(3):360–71.CrossRef Kalverda B, Pickersgill H, Shloma VV, Fornerod M. Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm. Cell. 2010;140(3):360–71.CrossRef
23.
go back to reference Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer MW. Dynamic association of NUP98 with the human genome. PLoS Genet. 2013;9(2):e1003308.CrossRef Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer MW. Dynamic association of NUP98 with the human genome. PLoS Genet. 2013;9(2):e1003308.CrossRef
24.
go back to reference Light WH, Freaney J, Sood V, Thompson A, D'Urso A, Horvath CM, et al. A conserved role for human Nup98 in altering chromatin structure and promoting epigenetic transcriptional memory. PLoS Biol. 2013;11(3):e1001524.CrossRef Light WH, Freaney J, Sood V, Thompson A, D'Urso A, Horvath CM, et al. A conserved role for human Nup98 in altering chromatin structure and promoting epigenetic transcriptional memory. PLoS Biol. 2013;11(3):e1001524.CrossRef
25.
go back to reference Ptak C, Aitchison JD, Wozniak RW. The multifunctional nuclear pore complex: a platform for controlling gene expression. Curr Opin Cell Biol. 2014;28:46–53.CrossRef Ptak C, Aitchison JD, Wozniak RW. The multifunctional nuclear pore complex: a platform for controlling gene expression. Curr Opin Cell Biol. 2014;28:46–53.CrossRef
26.
go back to reference Chatel G, Fahrenkrog B. Nucleoporins: leaving the nuclear pore complex for a successful mitosis. Cell Signal. 2011;23(10):1555–62.CrossRef Chatel G, Fahrenkrog B. Nucleoporins: leaving the nuclear pore complex for a successful mitosis. Cell Signal. 2011;23(10):1555–62.CrossRef
27.
go back to reference Cross MK, Powers MA. Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK. Mol Biol Cell. 2011;22(5):661–72.CrossRef Cross MK, Powers MA. Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK. Mol Biol Cell. 2011;22(5):661–72.CrossRef
28.
go back to reference Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, et al. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet. 1996;12(2):154–8.CrossRef Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, et al. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet. 1996;12(2):154–8.CrossRef
29.
go back to reference Borrow J, Shearman AM, Stanton VP, Becher R, Collins T, Williams AJ, et al. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet. 1996;12(2):159–67.CrossRef Borrow J, Shearman AM, Stanton VP, Becher R, Collins T, Williams AJ, et al. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet. 1996;12(2):159–67.CrossRef
30.
go back to reference Xu S, Powers MA. Nuclear pore proteins and cancer. Semin Cell Dev Biol. 2009;20(5):620–30.CrossRef Xu S, Powers MA. Nuclear pore proteins and cancer. Semin Cell Dev Biol. 2009;20(5):620–30.CrossRef
31.
go back to reference Simon DN, Rout MP. Cancer and the nuclear pore complex. Adv Exp Med Biol. 2014;773:285–307.CrossRef Simon DN, Rout MP. Cancer and the nuclear pore complex. Adv Exp Med Biol. 2014;773:285–307.CrossRef
32.
go back to reference Funasaka T, Balan V, Raz A, Wong RW. Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking. Biochem Biophys Res Commun. 2013;434(1):155–61.CrossRef Funasaka T, Balan V, Raz A, Wong RW. Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking. Biochem Biophys Res Commun. 2013;434(1):155–61.CrossRef
33.
go back to reference Singer S, Zhao R, Barsotti AM, Ouwehand A, Fazollahi M, Coutavas E, et al. Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes. Mol Cell. 2012;48(5):799–810.CrossRef Singer S, Zhao R, Barsotti AM, Ouwehand A, Fazollahi M, Coutavas E, et al. Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes. Mol Cell. 2012;48(5):799–810.CrossRef
34.
go back to reference Synnott NC, Murray A, McGowan PM, Kiely M, Kiely PA, O'Donovan N, et al. Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer? Int J Cancer. 2017;140(1):234–46.CrossRef Synnott NC, Murray A, McGowan PM, Kiely M, Kiely PA, O'Donovan N, et al. Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer? Int J Cancer. 2017;140(1):234–46.CrossRef
35.
go back to reference Kim JY, Park K, Jung HH, Lee E, Cho EY, Lee KH, et al. Association between mutation and expression of TP53 as a potential prognostic Marker of triple-negative breast Cancer. Cancer Res Treat. 2016;48(4):1338–50.CrossRef Kim JY, Park K, Jung HH, Lee E, Cho EY, Lee KH, et al. Association between mutation and expression of TP53 as a potential prognostic Marker of triple-negative breast Cancer. Cancer Res Treat. 2016;48(4):1338–50.CrossRef
36.
go back to reference Bertheau P, Lehmann-Che J, Varna M, Dumay A, Poirot B, Porcher R, et al. p53 in breast cancer subtypes and new insights into response to chemotherapy. Breast. 2013;22(Suppl 2):S27–9.CrossRef Bertheau P, Lehmann-Che J, Varna M, Dumay A, Poirot B, Porcher R, et al. p53 in breast cancer subtypes and new insights into response to chemotherapy. Breast. 2013;22(Suppl 2):S27–9.CrossRef
37.
go back to reference Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, et al. p53 status and the efficacy of cancer therapy in vivo. Science. 1994;266(5186):807–10.CrossRef Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, et al. p53 status and the efficacy of cancer therapy in vivo. Science. 1994;266(5186):807–10.CrossRef
38.
go back to reference O'Connor PM, Jackman J, Bae I, Myers TG, Fan S, Mutoh M, et al. Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Res. 1997;57(19):4285–300.PubMed O'Connor PM, Jackman J, Bae I, Myers TG, Fan S, Mutoh M, et al. Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Res. 1997;57(19):4285–300.PubMed
39.
go back to reference Fan S, Cherney B, Reinhold W, Rucker K, O'Connor PM. Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after taxol or vincristine treatment. Clin Cancer Res. 1998;4(4):1047–54.PubMed Fan S, Cherney B, Reinhold W, Rucker K, O'Connor PM. Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after taxol or vincristine treatment. Clin Cancer Res. 1998;4(4):1047–54.PubMed
40.
go back to reference Wahl AF, Donaldson KL, Fairchild C, Lee FY, Foster SA, Demers GW, et al. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med. 1996;2(1):72–9.CrossRef Wahl AF, Donaldson KL, Fairchild C, Lee FY, Foster SA, Demers GW, et al. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med. 1996;2(1):72–9.CrossRef
41.
go back to reference Bonnefoi H, Piccart M, Bogaerts J, Mauriac L, Fumoleau P, Brain E, et al. TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial. Lancet Oncol. 2011;12(6):527–39.CrossRef Bonnefoi H, Piccart M, Bogaerts J, Mauriac L, Fumoleau P, Brain E, et al. TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial. Lancet Oncol. 2011;12(6):527–39.CrossRef
42.
go back to reference Bidard FC, Matthieu MC, Chollet P, Raoefils I, Abrial C, Dômont J, et al. p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes. Ann Oncol. 2008;19(7):1261–5.CrossRef Bidard FC, Matthieu MC, Chollet P, Raoefils I, Abrial C, Dômont J, et al. p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes. Ann Oncol. 2008;19(7):1261–5.CrossRef
43.
go back to reference Agudo D, Gómez-Esquer F, Martínez-Arribas F, Núñez-Villar MJ, Pollán M, Schneider J. Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer. Int J Cancer. 2004;109(5):717–20.CrossRef Agudo D, Gómez-Esquer F, Martínez-Arribas F, Núñez-Villar MJ, Pollán M, Schneider J. Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer. Int J Cancer. 2004;109(5):717–20.CrossRef
44.
go back to reference Tian C, Zhou S, Yi C. High NUP43 expression might independently predict poor overall survival in luminal a and in HER2+ breast cancer. Future Oncol. 2018. Tian C, Zhou S, Yi C. High NUP43 expression might independently predict poor overall survival in luminal a and in HER2+ breast cancer. Future Oncol. 2018.
Metadata
Title
NUP98 – a novel predictor of response to anthracycline-based chemotherapy in triple negative breast cancer
Authors
Paul B. Mullan
Victoria Bingham
Paula Haddock
Gareth W. Irwin
Elaine Kay
Stephen McQuaid
Niamh E. Buckley
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5407-9

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