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The cross-talk of cancer-associated fibroblasts assist in prognosis and immunotherapy in patients with breast carcinoma

Cancer Gene Therapy volume 29, pages 2001–2012 (2022)Cite this article

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Abstract

The association between cancer-associated fibroblasts (CAFs) and tumor microenvironment (TME) is a key factor in promoting tumor progression. However, the correlation between CAFs and TME in breast carcinoma has not been elucidated. Thus, further study about the cross-effect between CAFs and TME can provide novel strategies for breast carcinoma treatment, particularly targeted immunotherapy. First, we systematically analyzed cell communication in a single-cell dataset and identified the interacted genes between CAFs and TME components. Then, a robust fibroblast-related score (FRS) model was developed using the LASSO algorithm. The FRS can be a reliable adverse prognostic factor in three cohorts with breast carcinoma. Functional enrichment analysis and single-sample Gene Set Enrichment Analysis showed that patients with a high FRS had cold tumors with active proliferation and immunosuppression. Patients with a low FRS presented with hot tumors with active immune and cell-killing functions. Genomic variation analysis revealed that patients with a low FRS had a higher somatic mutation load and copy number variation burden. Finally, patients with a low FRS were more sensitive to chemotherapy and immunotherapy, particularly anti-PD-1 therapy. In conclusion, a reliable FRS model was constructed not only reliable for predicting prognosis but also competent to estimate clinical immunotherapy and chemotherapy response for patients with BRCA, which might provide significant clinical implications for guiding clinical decision-making for patients with BRCA.

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Fig. 1: Schematic flowchart showed the analysis strategy.
Fig. 2: Single-cell map of CAFs.
Fig. 3: Genomic map of FRGs in BRCA.
Fig. 4: Construction of the T-regs-related risk model.
Fig. 5: Verification of the FRG-related risk model.
Fig. 6: Functional analysis of FRS.
Fig. 7: Immunoinfiltration analysis of FRS.
Fig. 8: Genomic variation landscape of FRS.
Fig. 9: FRS-related risk models can guide clinical treatment decision-making.

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Data availability

The raw data mentioned in this study can be downloaded from online databases. More detailed information can be provided by the corresponding author upon reasonable request.

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Acknowledgements

We thank all the participants who supported our study. In particular, thanks to the TCGA database and GEO database for the analytical data.

Funding

This work was supported by the Youth Found of Natural Science Foundation of Jiangsu Province (BK20200395) and the Clinical Medical Science and Technology Development Fund Project of Jiangsu University (JLY20180103).

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Author notes

  1. These authors contributed equally: Xuyu Gu, Shiya Zheng, Haifeng Zhang.

Authors and Affiliations

  1. School of Medicine, Southeast University, Nanjing, 210009, China

    Xuyu Gu, Haifeng Zhang & Xiaotong Sun

  2. Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China

    Shiya Zheng

  3. Department of Breast Surgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu, 215300, China

    Qin Zhou

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Contributions

XG analyzed the data and wrote the manuscript. SZ and HZ was the co- first author, and provided specialized expertise and collaboration in data analysis. XS carried out data interpretations and helped data discussion. QZ conceived and designed the whole project and drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Qin Zhou.

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Gu, X., Zheng, S., Zhang, H. et al. The cross-talk of cancer-associated fibroblasts assist in prognosis and immunotherapy in patients with breast carcinoma. Cancer Gene Ther 29, 2001–2012 (2022). https://doi.org/10.1038/s41417-022-00514-w

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