Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Sep 8;9(20):3736-3742.
doi: 10.7150/jca.28054. eCollection 2018.

Activated Tumor-infiltrating Fibroblasts Predict Worse Prognosis in Breast Cancer Patients

Guoming Hu  1 , Feng Xu  1 , Kefang Zhong  1 , Shimin Wang  2 , Liming Huang  1 , Wei Chen  1
Affiliations

Activated Tumor-infiltrating Fibroblasts Predict Worse Prognosis in Breast Cancer Patients

Guoming Hu et al. J Cancer. .

Abstract

Purpose: Activated tumor-infiltrating fibroblasts were significantly associated with survival of cancer patients. However, they are heterogeneous population, and the prognostic role of these cells in human breast cancer still remains controversial. Herein, we performed the meta-analysis to better understand the role of these cells in prognosis prediction for breast cancer patients. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral activated fibroblast density detected by immunohistochemical (IHC) method and overall survival (OS) and/or disease-free survival (DFS) in breast cancer patients, then computed extracted data into hazard ratios (HRs) for OS, DFS and clinicopathological features such as lymph node metastasis, TNM stage with STATA 12.0. Results: A total of 3680 patients with breast cancer from 15 published studies were incorporated into this meta-analysis. We found that the infiltration of activated fibroblasts significantly decreased overall survival (OS) and disease-free survival (DFS) in patients. In stratified analyses, high density of FSP-1+ or podoplanin+ fibroblasts was significantly associated with worse OS; while α-SMA+ or podoplanin+ fibroblast infiltration was associated with worse DFS in breast cancer. In addition, elevated number of activated tumor-infiltrating fibroblasts significantly correlated with lymph node metastasis and poor tumor differentiation of patients. Conclusion: The infiltration of activated fibroblasts, especially the FSP-1+ or podoplanin+ fibroblasts leads to worse clinical outcome in breast cancer patients, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment.

Keywords: activated fibroblasts; breast cancer; meta-analysis; prognosis; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Fig 1
Fig 1
Forest plots describing HR of the association between activated fibroblast infiltration and OS in breast cancer patients.
Fig 2
Fig 2
Stratified analyses describing HRs of the association between the infiltration of different subpopulations of activated fibroblasts and OS.
Fig 3
Fig 3
Forest plots describing HR of the association between activated fibroblast infiltration and DFS in breast cancer patients.
Fig 4
Fig 4
Stratified analyses describing HRs of the association between the infiltration of different subpopulations of activated fibroblasts and DFS.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA: a cancer journal for clinicians. 2018;68(1):7–30. - PubMed
    1. Motz GT, Coukos G. The parallel lives of angiogenesis and immunosuppression: cancer and other tales. Nat Rev Immunol. 2011;11(10):702–711. - PubMed
    1. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nature reviews Cancer. 2006;6(5):392–401. - PubMed
    1. Ohlund D, Elyada E, Tuveson D. Fibroblast heterogeneity in the cancer wound. J Exp Med. 2014;211(8):1503–1523. - PMC - PubMed
    1. Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science. 2010;330(6005):827–830. - PubMed