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HSF1 expression in tumor-associated macrophages promotes tumor cell proliferation and indicates poor prognosis in esophageal squamous cell carcinoma

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Abstract

Purpose

Tumor-associated macrophages (TAMs), are crucial for the survival and development of tumor cells. Heat shock factor 1 (HSF1) is a potent, complex carcinogenesis modulator, and esophageal cancer (EC) patients have a bad prognosis when HSF1 is highly expressed. HSF1's clinical importance and biological role in TAMs are still unknown.

Methods

The HSF1 expression profile and patient survival information were analyzed from the TCGA database. The infiltration of different types of immune cells in EC was evaluated based on HSF1 gene expression by Sangerbox 3.0. Immunochemistry was employed to assess HSF1 protein expression in 134 individuals with esophageal squamous cell carcinoma (ESCC), proceeded by association with clinicopathological variables. The role of macrophage-driven HSF1 were observed using HSF1-knockdown THP1 cells.

Results

High level of HSF1 have a poorer prognosis in individuals with EC. The expressing level of HSF1 was positively related to infiltration of M2 macrophages (P < 0.05). The expression of HSF1 in macrophages was an independent factor for DFS (P = 0.002) and OS (P = 0.002) in ESCC cases. HSF1 was up-regulated in IL-4 stimulation THP1 cells in a time-dependent manner. Under the heat stimulation condition, THP1-derived macrophages were more sensitive than tumor cells. Compared to IL-4 induced-THP1 cells control, the HSF1 knockdown in THP1 cell inhibited the growth and proliferation of ESCC cells.

Conclusions

The up-regulation of HSF1 was more rapid and could affect the proliferation of tumor cells in IL4-induced macrophages. The expression of HSF1 in TAMs can also serve as a marker for ESCC prognosis.

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Funding

This work was supported by the National Natural Science Foundation of Guangdong Province (No. 2019A1515010500).

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Authors and Affiliations

  1. Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, No. 132 Waihuandong Road, University Town, Guangzhou, 510006, China

    Yiqiu Li, Qifan Li, Jiasheng Liu, Yuying Huang, Jinzhu Mao & Ge Zhang

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  1. Yiqiu Li
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  2. Qifan Li
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  3. Jiasheng Liu
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  4. Yuying Huang
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  5. Jinzhu Mao
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  6. Ge Zhang
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Contributions

Study concept and design: GZ, YL; acquisition of data: YL, QL, YH, JL; analysis and interpretation of data: YH, JM; drafting of the manuscript: YL, GZ; critical revision of the manuscript for important intellectual content: GZ; statistical analysis: YL, GZ.

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Correspondence to Ge Zhang.

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The authors declare that they have no competing interests.

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The Institutional Review Board of Sun Yat-Sen University Cancer Center approved this study.

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Li, Y., Li, Q., Liu, J. et al. HSF1 expression in tumor-associated macrophages promotes tumor cell proliferation and indicates poor prognosis in esophageal squamous cell carcinoma. Clin Transl Oncol 25, 1682–1689 (2023). https://doi.org/10.1007/s12094-022-03063-8

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  • DOI: https://doi.org/10.1007/s12094-022-03063-8

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