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

Abstract

Background

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

Methods

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.

Results

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.

Conclusions

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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Funding

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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Correspondence to Chi Zhang.

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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). https://doi.org/10.1007/s12282-020-01101-3

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Keywords

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