Novel module and hub genes of distinctive breast cancer associated fibroblasts identified by weighted gene co‐expression network analysis



As abundant and heterogeneous stromal cells in tumor microenvironment, carcinoma-associated fibroblasts (CAFs) are critically involved in cancer progression.


To identify co-expression module and hub genes of distinctive breast CAFs, weighted gene co-expression network analysis (WGCNA) was conducted based on the expression array results of CAFs from seven chemo-sensitive breast cancer (BC) patients and seven chemo-resistant ones before neo-adjuvant chemotherapy.


A total of 4916 genes were included in WGCNA, and 12 modules were determined. Module-trait assay showed that the blue module (cor = 0.97, P < 0.001) was associated with CAF-related chemo-resistance, which was enriched mainly as “inflammatory response”, “interferon-gamma-mediated signaling” and “NIK/NF-kappaB signaling” pathways. Moreover, CXCL8, CXCL10, CXCL11, PLSCR1, RIPK2 and USP18 were found to be potentially associated with chemo-resistance related to CAFs and prognosis of BC.


Our current data offered valuable insights into the molecular mechanisms of distinctive breast CAFs, which was beneficial for revealing how chemo-resistance of BC was initiated.

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  1. 1.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  Google Scholar 

  2. 2.

    Mabe NW, Fox DB, Lupo R, Decker AE, Phelps SN, Thompson JW, et al. Epigenetic silencing of tumor suppressor Par-4 promotes chemoresistance in recurrent breast cancer. J Clin Invest. 2018;128:4413–28.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582–98.

    CAS  PubMed  Google Scholar 

  4. 4.

    Sugimoto H, Mundel TM, Kieran MW, Kalluri R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther. 2006;5:1640–6.

    CAS  PubMed  Google Scholar 

  5. 5.

    Paulsson J, Ryden L, Strell C, Frings O, Tobin NP, Fornander T, et al. High expression of stromal PDGFRbeta is associated with reduced benefit of tamoxifen in breast cancer. J Pathol Clin Res. 2017;3:38–433.

    CAS  PubMed  Google Scholar 

  6. 6.

    Ruhland MK, Loza AJ, Capietto AH, Luo X, Knolhoff BL, Flanagan KC, et al. Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat Commun. 2016;7:11762.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Su S, Chen J, Yao H, Liu J, Yu S, Lao L, et al. CD10(+)GPR77(+) Cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell. 2018;172(841–856):e816.

    Google Scholar 

  8. 8.

    Li Y, Ma X, Zhao J, Xu J, Shi J, Zhu XG, et al. Developmental genetic mechanisms of C4 syndrome based on transcriptome analysis of C3 cotyledons and C4 assimilating shoots in Haloxylon ammodendron. PLoS ONE. 2015;10:e0117175.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Liu F, Yang Y, Gao J, Ma C, Bi Y. A comparative transcriptome analysis of a wild purple potato and its red mutant provides insight into the mechanism of anthocyanin transformation. PLoS ONE. 2018;13:e0191406.

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Liu F, Jin Z, Wang Y, Bi Y, Melton JT 3rd. Plastid genome of dictyopteris divaricata (Dictyotales, Phaeophyceae): understanding the evolution of plastid genomes in brown algae. Mar Biotechnol (NY). 2017;19:627–37.

    CAS  Google Scholar 

  11. 11.

    Shan SJ, Liu DZ, Wang L, Zhu YY, Zhang FM, Li T, et al. Identification and expression analysis of irak1 gene in common carp Cyprinus carpio L.: indications for a role of antibacterial and antiviral immunity. J Fish Biol. 2015;87:241–55.

    CAS  PubMed  Google Scholar 

  12. 12.

    Sun G, Pan J, Liu K, Wang S, Wang X, Wang X. Molecular cloning and expression analysis of P-selectin glycoprotein ligand-1 from zebrafish (Danio rerio). Fish Physiol Biochem. 2012;38:555–64.

    CAS  PubMed  Google Scholar 

  13. 13.

    Yuan F, Lyu MJ, Leng BY, Zhu XG, Wang BS. The transcriptome of NaCl-treated Limonium bicolor leaves reveals the genes controlling salt secretion of salt gland. Plant Mol Biol. 2016;91:241–56.

    CAS  PubMed  Google Scholar 

  14. 14.

    Zhu YY, Xing WX, Shan SJ, Zhang SQ, Li YQ, Li T, et al. Characterization and immune response expression of the Rig-I-like receptor mda5 in common carp Cyprinus carpio. J Fish Biol. 2016;88:2188–202.

    CAS  PubMed  Google Scholar 

  15. 15.

    Jiang CY, Tholen D, Xu JM, Xin CP, Zhang H, Zhu XG, et al. Increased expression of mitochondria-localized carbonic anhydrase activity resulted in an increased biomass accumulation in Arabidopsis thaliana. J Plant Biol. 2014;57:366–74.

    CAS  Google Scholar 

  16. 16.

    Zhang Z, Zhang L, Wang B, Zhu X, Zhao L, Chu C, et al. RNF144B inhibits LPS-induced inflammatory responses via binding TBK1. J Leukoc Biol. 2019;106:1303–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Mosig RA, Lin L, Senturk E, Shah H, Huang F, Schlosshauer P, et al. Application of RNA-Seq transcriptome analysis: CD151 is an Invasion/Migration target in all stages of epithelial ovarian cancer. J Ovarian Res. 2012;5:4.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Ding NZ, Qi QR, Gu XW, Zuo RJ, Liu J, Yang ZM. De novo synthesis of sphingolipids is essential for decidualization in mice. Theriogenology. 2018;106:227–36.

    CAS  PubMed  Google Scholar 

  19. 19.

    Zhang Z, Zhang L, Wang B, Wei R, Wang Y, Wan J, et al. MiR-337-3p suppresses proliferation of epithelial ovarian cancer by targeting PIK3CA and PIK3CB. Cancer Lett. 2020;469:54–67.

    CAS  PubMed  Google Scholar 

  20. 20.

    Yuan F, Lyu MJ, Leng BY, Zheng GY, Feng ZT, Li PH, et al. Comparative transcriptome analysis of developmental stages of the Limonium bicolor leaf generates insights into salt gland differentiation. Plant Cell Environ. 2015;38:1637–57.

    CAS  PubMed  Google Scholar 

  21. 21.

    Li L, Yang HJ, Liu DC, He HB, Wang CF, Zhong JF, et al. Analysis of biofilms formation and associated genes detection in Staphylococcus isolates from bovine mastitis. Int J Appl Res Vet Med. 2012;10:62–8.

    CAS  Google Scholar 

  22. 22.

    Liu M, Xie SB, Zhou J. Use of animal models for the imaging and quantification of angiogenesis. Exp Anim. 2018;67:1–6.

    CAS  PubMed  Google Scholar 

  23. 23.

    Liu XY, Ju ZH, Wang LL, Zhang Y, Huang JM, Li QL, et al. Six novel single-nucleotide polymorphisms in SPAG11 gene and their association with sperm quality traits in Chinese Holstein bulls. Anim Reprod Sci. 2011;129:14–211.

    CAS  PubMed  Google Scholar 

  24. 24.

    Lou MF, Zhang XY, Fu RS, Wang DH. Effects of dietary fiber content on energetics in nonreproductive and reproductive Brandt's voles (Lasiopodomys brandtii). Can J Zool. 2015;93:251–8.

    CAS  Google Scholar 

  25. 25.

    Meng XQ, Dai YY, Jing LD, Bai J, Liu SZ, Zheng KG, et al. Subcellular localization of proline-rich tyrosine kinase 2 during oocyte fertilization and early-embryo development in mice. J Reprod Dev. 2016;62:351–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Xie W, Zhou J. Aberrant regulation of autophagy in mammalian diseases. Biol Lett. 2018;2018:14.

    Google Scholar 

  27. 27.

    Li H, Yang GW, Ma F, Li T, Yang HT, Rombout J, et al. Molecular characterization of a fish-specific toll-like receptor 22 (TLR22) gene from common carp (Cyprinus carpio L.): evolutionary relationship and induced expression upon immune stimulants. Fish Shellfish Immunol. 2017;63:74–86.

    CAS  PubMed  Google Scholar 

  28. 28.

    Li T, Li H, Peng SQ, Zhang FM, An LG, Yang GW. Molecular characterization and expression pattern of X box-binding protein-1 (XBP1) in common carp (Cyprinus carpio L.): indications for a role of XBP1 in antibacterial and antiviral immunity. Fish Shellfish Immunol. 2017;67:667–74.

    CAS  PubMed  Google Scholar 

  29. 29.

    Rombout J, Yang GW, Kiron V. Adaptive immune responses at mucosal surfaces of teleost fish. Fish Shellfish Immunol. 2014;40:634–43.

    CAS  PubMed  Google Scholar 

  30. 30.

    Shan SJ, Liu DZ, Liu RR, Zhu YY, Li T, Zhang FM, et al. Non-mammalian toll-like receptor 18 (Tlr18) recognizes bacterial pathogens in common carp (Cyprinus carpio L.): Indications for a role of participation in the NF-kappa B signaling pathway. Fish Shellfish Immunol. 2018;72:187–98.

    CAS  PubMed  Google Scholar 

  31. 31.

    Yang GW, Guo HY, Li H, Shan SJ, Zhang XQ, Rombout J, et al. Molecular characterization of LEAP-2 cDNA in common carp (Cyprinus carpio L.) and the differential expression upon a Vibrio anguillarum stimulus; indications for a significant immune role in skin. Fish Shellfish Immunol. 2014;37:22–9.

    PubMed  Google Scholar 

  32. 32.

    Yang HT, Zou SS, Zhai LJ, Wang Y, Zhang FM, An LG, et al. Pathogen invasion changes the intestinal microbiota composition and induces innate immune responses in the zebrafish intestine. Fish Shellfish Immunol. 2017;71:35–42.

    CAS  PubMed  Google Scholar 

  33. 33.

    Zhang FM, Liu DZ, Wang L, Li T, Chang Q, An LG, et al. Characterization of IgM-binding protein: A pIgR-like molecule expressed by intestinal epithelial cells in the common carp (Cyprinus carpio L.). Vet Immunol Immunopathol. 2015;167:30–5.

    CAS  PubMed  Google Scholar 

  34. 34.

    Hou PL, Wang HM, Zhao GM, He CQ, He HB. Rapid detection of infectious bovine Rhinotracheitis virus using recombinase polymerase amplification assays. BMC Vet Res. 2017;2017:13.

    Google Scholar 

  35. 35.

    Zhang L, Tan Y, Fan S, Zhang X, Zhang Z. Phylostratigraphic analysis of gene co-expression network reveals the evolution of functional modules for ovarian cancer. Sci Rep. 2019;9:2623.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Zhang L, Zhang X, Fan S, Zhang Z. Identification of modules and hub genes associated with platinum-based chemotherapy resistance and treatment response in ovarian cancer by weighted gene co-expression network analysis. Med (Baltim). 2019;98:e17803.

    CAS  Google Scholar 

  37. 37.

    Selvaraj G, Kaliamurthi S, Kaushik AC, Khan A, Wei YK, Cho WC, et al. Identification of target gene and prognostic evaluation for lung adenocarcinoma using gene expression meta-analysis, network analysis and neural network algorithms. J Biomed Inform. 2018;86:120–34.

    PubMed  Google Scholar 

  38. 38.

    Wang FR, Xu ZZ, Sun R, Gong YC, Liu GD, Zhang JX, et al. Genetic dissection of the introgressive genomic components from Gossypium barbadense L. that contribute to improved fiber quality in Gossypium hirsutum L. Mol Breed. 2013;32:547–62.

    Google Scholar 

  39. 39.

    Pang CH, Li K, Wang BS. Overexpression of SsCHLAPXs confers protection against oxidative stress induced by high light in transgenic Arabidopsis thaliana. Physiol Plant. 2011;143:355–66.

    CAS  PubMed  Google Scholar 

  40. 40.

    Zhang Z, Zhao L, Wei X, Guo Q, Zhu X, Wei R, et al. Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML. Oncol Lett. 2018;16:5147–59.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Zhang XY, Lou MF, Shen W, Fu RS, Wang DH. A maternal low-fiber diet predisposes offspring to improved metabolic phenotypes in adulthood in an herbivorous rodent. Physiol Biochem Zool. 2017;90:75–84.

    PubMed  Google Scholar 

  42. 42.

    Tian W, Zhang HY, Zhang J, Zhao L, Miao MS, Huang H. Responses of zooplankton community to environmental factors and phytoplankton biomass in lake Nansihu. China Pak J Zool. 2017;49:493–504.

    Google Scholar 

  43. 43.

    Zheng S, Shi J, Wu X, Peng Z, Xin C, Zhang L, et al. Presence of Torque teno sus virus 1 and 2 in porcine circovirus 3-positive pigs. Transbound Emerg Dis. 2018;65:327–30.

    CAS  PubMed  Google Scholar 

  44. 44.

    Zhu YY, Qi CC, Shan SJ, Zhang FM, Li H, An LG, et al. Characterization of common carp (Cyprinus carpio L.) interferon regulatory factor 5 (IRF5) and its expression in response to viral and bacterial challenges. BMC Vet Res. 2016;2016:12.

    Google Scholar 

  45. 45.

    Li YY, Xu JJ, Ul Haq N, Zhang H, Zhu XG. Was low CO2 a driving force of C-4 evolution: Arabidopsis responses to long-term low CO2 stress. J Exp Bot. 2014;65:3657–67.

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Zhang YJ, Kong XQ, Dai JL, Luo Z, Li ZH, Lu HQ, et al. Global gene expression in cotton (Gossypium hirsutum L.) leaves to waterlogging stress. PLoS ONE. 2017;2017:12.

    Google Scholar 

  47. 47.

    Liu QQ, Liu RR, Ma YC, Song J. Physiological and molecular evidence for Na+ and Cl- exclusion in the roots of two Suaeda salsa populations. Aquat Bot. 2018;146:1–7.

    CAS  Google Scholar 

  48. 48.

    Zhou JC, Zhao WW, Yin CH, Song J, Wang BS, Fan JL, et al. The role of cotyledons in the establishment of Suaeda physophora seedlings. Plant Biosyst. 2014;148:584–90.

    Google Scholar 

  49. 49.

    Wang XJ, Ju ZH, Huang JM, Hou MH, Zhou L, Qi C, et al. The relationship between the variants of the bovine MBL2 gene and milk production traits, mastitis, serum MBL-C levels and complement activity. Vet Immunol Immunopathol. 2012;148:311–9.

    CAS  PubMed  Google Scholar 

  50. 50.

    Chen M, Song J, Wang BS. NaCl increases the activity of the plasma membrane H+-ATPase in C-3 halophyte Suaeda salsa callus. Acta Physiol Plant. 2010;32:27–36.

    Google Scholar 

  51. 51.

    Chen TS, Yuan F, Song J, Wang BS. Nitric oxide participates in waterlogging tolerance through enhanced adventitious root formation in the euhalophyte Suaeda salsa. Funct Plant Biol. 2016;43:244–53.

    CAS  PubMed  Google Scholar 

  52. 52.

    Sui N, Wang Y, Liu SS, Yang Z, Wang F, Wan SB. Transcriptomic and physiological evidence for the relationship between unsaturated fatty acid and salt stress in peanut. Front Plant Sci. 2018;9:12.

    Google Scholar 

  53. 53.

    Sui N, Han GL. Salt-induced photoinhibition of PSII is alleviated in halophyte Thellungiella halophila by increases of unsaturated fatty acids in membrane lipids. Acta Physiol Plant. 2014;36:983–92.

    CAS  Google Scholar 

  54. 54.

    Ding F, Chen M, Sui N, Wang BS. Ca2+ significantly enhanced development and salt-secretion rate of salt glands of Limonium bicolor under NaCl treatment. S Afr J Bot. 2010;76:95–101.

    CAS  Google Scholar 

  55. 55.

    Qi YC, Wang FF, Zhang H, Liu WQ. Overexpression of suadea salsa S-adenosylmethionine synthetase gene promotes salt tolerance in transgenic tobacco. Acta Physiol Plant. 2010;32:263–9.

    CAS  Google Scholar 

  56. 56.

    Sui N, Li M, Li K, Song J, Wang BS. Increase in unsaturated fatty acids in membrane lipids of Suaeda salsa L. enhances protection of photosystem II under high salinity. Photosynthetica. 2010;48:623–9.

    CAS  Google Scholar 

  57. 57.

    Selvaraj G, Kaliamurthi S, Lin S, Gu K, Wei DQ. Prognostic impact of tissue inhibitor of metalloproteinase-1 in non- small cell lung cancer: systematic review and meta-analysis. Curr Med Chem. 2019;26:7694–713.

    CAS  PubMed  Google Scholar 

  58. 58.

    Wei DQ, Selvaraj G, Kaushik AC. Computational perspective on the current state of the methods and new challenges in cancer drug discovery. Curr Pharm Des. 2018;24:3725–6.

    CAS  PubMed  Google Scholar 

  59. 59.

    Zhang LY, Zhang XJ, Fan SJ. Meta-analysis of salt-related gene expression profiles identifies common signatures of salt stress responses in Arabidopsis. Plant Syst Evol. 2017;303:757–74.

    CAS  Google Scholar 

  60. 60.

    Zhang XH, Jin X, Malladi S, Zou Y, Wen YH, Brogi E, et al. Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell. 2013;154:1060–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, et al. Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nat Med. 2018;24:463–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Kuan EL, Ziegler SF. A tumor-myeloid cell axis, mediated via the cytokines IL-1alpha and TSLP, promotes the progression of breast cancer. Nat Immunol. 2018;19:366–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Weichand B, Popp R, Dziumbla S, Mora J, Strack E, Elwakeel E, et al. S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1beta. J Exp Med. 2017;214:2695–713.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Perez-Yepez EA, Ayala-Sumuano JT, Lezama R, Meza I. A novel beta-catenin signaling pathway activated by IL-1beta leads to the onset of epithelial-mesenchymal transition in breast cancer cells. Cancer Lett. 2014;354:164–71.

    CAS  PubMed  Google Scholar 

  65. 65.

    Singh JK, Farnie G, Bundred NJ, Simoes BM, Shergill A, Landberg G, et al. Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and -independent mechanisms. Clin Cancer Res. 2013;19:643–56.

    CAS  PubMed  Google Scholar 

  66. 66.

    Al-Harbi B, Hendrayani SF, Silva G, Aboussekhra A. Let-7b inhibits cancer-promoting effects of breast cancer-associated fibroblasts through IL-8 repression. Oncotarget. 2018;9:17825–38.

    PubMed  PubMed Central  Google Scholar 

  67. 67.

    Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 2010;120:485–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Lee HW, Choi HJ, Ha SJ, Lee KT, Kwon YG. Recruitment of monocytes/macrophages in different tumor microenvironments. Biochim Biophys Acta. 2013;1835:170–9.

    CAS  PubMed  Google Scholar 

  69. 69.

    Gok Yavuz B, Gunaydin G, Gedik ME, Kosemehmetoglu K, Karakoc D, Ozgur F, et al. Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1(+) TAMs. Sci Rep. 2019;9:3172.

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    Johnstone CN, Chand A, Putoczki TL, Ernst M. Emerging roles for IL-11 signaling in cancer development and progression: focus on breast cancer. Cytokine Growth Factor Rev. 2015;26:489–98.

    CAS  PubMed  Google Scholar 

  71. 71.

    Stickeler E, Pils D, Klar M, Orlowsk-Volk M, Zur Hausen A, Jager M, et al. Basal-like molecular subtype and HER4 up-regulation and response to neoadjuvant chemotherapy in breast cancer. Oncol Rep. 2011;26:1037–45.

    CAS  PubMed  Google Scholar 

  72. 72.

    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;13:3207–14.

    CAS  PubMed  Google Scholar 

  73. 73.

    Sotiriou C, Lacroix M, Lespagnard L, Larsimont D, Paesmans M, Body JJ. Interleukins-6 and -11 expression in primary breast cancer and subsequent development of bone metastases. Cancer Lett. 2001;169:87–95.

    CAS  PubMed  Google Scholar 

  74. 74.

    Zhou Q, Ben-Efraim I, Bigcas JL, Junqueira D, Wiedmer T, Sims PJ. Phospholipid scramblase 1 binds to the promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene to enhance its expression. J Biol Chem. 2005;280:35062–8.

    CAS  PubMed  Google Scholar 

  75. 75.

    Choi HJ, Lui A, Ogony J, Jan R, Sims PJ, Lewis-Wambi J. Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death. Breast Cancer Res. 2015;17:6.

    PubMed  PubMed Central  Google Scholar 

  76. 76.

    Singel SM, Batten K, Cornelius C, Jia G, Fasciani G, Barron SL, et al. Receptor-interacting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways. Breast Cancer Res. 2014;16:R28.

    PubMed  PubMed Central  Google Scholar 

  77. 77.

    Tan Y, Zhou G, Wang X, Chen W, Gao H. USP18 promotes breast cancer growth by upregulating EGFR and activating the AKT/Skp2 pathway. Int J Oncol. 2018;53:371–83.

    CAS  PubMed  Google Scholar 

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This work was supported by National Natural Science Foundation of China (81601442, 31800185), and the Primary Research & Development Plan of Shandong Province (2017GSF218013) and A Project of Shandong Province Higher Educational Science and Technology Program (J18KA147).

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Xu, Y., Zhang, Z., Zhang, L. et al. Novel module and hub genes of distinctive breast cancer associated fibroblasts identified by weighted gene co‐expression network analysis. Breast Cancer 27, 1017–1028 (2020).

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  • Breast cancer
  • Chemo-resistance
  • Gene expression
  • Inflammation