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  3. Exploring the association of POSTN+ cancer-associated fibroblasts with triple-negative breast cancer

Exploring the association of POSTN+ cancer-associated fibroblasts with triple-negative breast cancer

  • Int J Biol Macromol. 2024 May;268(Pt 1):131560. doi: 10.1016/j.ijbiomac.2024.131560.
Shuangyan Lin 1,  Miaoni Zhou 2,  Liying Cheng 3,  Zhifeng Shuai 4,  Mingyuan Zhao 4,  Ruixia Jie 4,  Qun Wan 5,  Fang Peng 6,  Shiping Ding 7
Affiliations

Affiliations

  • 1 Department of Cell Biology and Department of Cardiovascular Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 57 Zhugan Lane, Hangzhou 310000, Zhejiang, China; Department of Pathology, Zhejiang Hospital, Zhejiang University School of Medicine, 12 Lingyin Rd, Hangzhou 310013, Zhejiang, China.
  • 2 Department of Dermatology, Hangzhou Third People's Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, 38 Xihu Rd, Hangzhou 310009, Zhejiang, China.
  • 3 Jiaxing University Medical College, 899 Shiguang Rd, Jiaxing 314001, Zhejiang, China.
  • 4 Department of Pathology, Zhejiang Hospital, 12 Lingyin Rd, Hangzhou 310013, Zhejiang, China.
  • 5 Department of Urinary Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003, Zhejiang, China.
  • 6 Department of Pathology, Zhejiang Hospital, 12 Lingyin Rd, Hangzhou 310013, Zhejiang, China. Electronic address: pengfang999@139.com.
  • 7 Department of Cell Biology and Department of Cardiovascular Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 57 Zhugan Lane, Hangzhou 310000, Zhejiang, China; Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, China. Electronic address: dingshiping@zju.edu.cn.
PMID: 38631570 DOI: 10.1016/j.ijbiomac.2024.131560
Abstract

Triple-negative breast Cancer (TNBC) is a subtype of breast Cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) play a critical role in regulating TNBC tumor development. This study aimed to identify and characterize a specific subtype of CAFs associated with TNBC. Initially, using high-throughput bulk transcriptomic data in two cohorts, we identified three CAF-related subtypes (CS1, CS2, CS3) in TNBC samples. These three CAFs subtypes were closely linked to the tumor microenvironment. The CS1 subtype exhibited a relatively immune-rich microenvironment and a favourable prognosis, whereas the CS3 subtype displayed an immune-deprived tumor microenvironment and an unfavourable prognosis. Through WGCNA analysis, POSTN was identified as a key biomarker for CAFs associated with TNBC. Then, POSTN+CAFs was identified and characterized. Both POSTN and POSTN+CAFs showed significant positive correlations with stromal molecules HGF and MET at both the transcriptional and protein levels. Specifically co-localized with CAFs in the tumor stromal area, POSTN, produced by POSTN+CAFs, could modulate the HGF-MET axis, serving as a bypass activation pathway to regulate tumor cell proliferation in response to EGFR inhibitor and Met Inhibitor. This study underscores the significance of POSTN and POSTN+CAFs as crucial targets for the diagnosis and treatment of TNBC.

Keywords

Cancer-associated fibroblasts; POSTN(+)CAFs; Triple-negative breast cancer.

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