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

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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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Authors and Affiliations

  1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

    Yangguang Xu

  2. Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

    Chi Zhang

  3. Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China

    Zhen Zhang

  4. Key Lab of Plant Stress Research, College of Life Science, Shandong Normal University, Jinan, 250014, Shandong, China

    Luoyan Zhang

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  1. Yangguang Xu
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12282_2020_1101_MOESM2_ESM.xlsx

Table S1: Information of the genes in the resistance-related blue module, including genes’ ID, genes’ names, genes’ degree in each module and genes’ expression FC between resistant and sensitive samples (XLSX 17 kb)

Table S2: The GO enrichment result of the genes in the resistance-related blue module (XLSX 28 kb)

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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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