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HS6ST1 overexpressed in cancer-associated fibroblast and inhibited cholangiocarcinoma progression

  • Author Footnotes
    1 These authors contributed equally to this work.
    Sheng Hu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Chuqi Xia
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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  • Hao Zou
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
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  • Wenjun Ren
    Affiliations
    Department of Thoracic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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  • Lixin Liu
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
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  • Lianmin Wang
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
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  • Qiang Kang
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
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  • Kai He
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
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  • Tao Wang
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
    Search for articles by this author
  • Xiaowen Zhang
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374# Dianmian Avenue, Kunming, Yunnan 650101, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
Published:December 29, 2022DOI:https://doi.org/10.1016/j.dld.2022.12.007

      Abstract

      Backgroud

      Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumor microenvironment, which play an important role in tumor progression. However, the mechanism is unclear.

      Aims

      To investigate the role of CAFs with HS6ST1-overexpression in cell migration and invasion effects.

      Methods

      Human primary CAFs were isolated and identified from intrahepatic cholangiocarcinoma. mRNA profiles differences between CAFs and NFs were examined by using transcriptome sequencing. Using Transwell® migration assays, ICCA cells (RBE and HUCCT1) with NF-CM, CAF-CM, CAFsNC-CM, and CAFsHS6ST1-CM were analyzed. Immunohistochemical staining were used to analyze the expression of HS6ST1 in CAF in 152 patients with ICCA. Overall survival (OS) was compared based on CAF HS6ST1 expression were analysed. The relationship between clinicopathological parameters and survival was also examined.

      Results

      Successfully isolated CAFs is positive staining with αSMA, FSP-1, FAP, and PDGFR-β. Transcriptome sequencing showed that differently expressed genes were enriched in the function of the extracellular matrix and chemokine signaling pathway. HS6ST1 is differentially expressed between CAFs and NFs, and associated with the migration and invasion of ICCA cells. Moreover, HS6ST1 positive expression of CAFs predicted unfavorable prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation with the presence of lymph node metastasis.

      Conclusion

      HS6ST1 is new possibilities for targeting the CAFs to reduce cholangiocarcinoma growth and metastasis.

      Keywords

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