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FAM83H overexpression predicts worse prognosis and correlates with less CD8+ T cells infiltration and Ras-PI3K-Akt-mTOR signaling pathway in pancreatic cancer

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Abstract

Background

Family with sequence similarity 83 members H (FAM83H) is one member of Family with sequence similarity 83 (FAM83) family, which possess oncogenic properties in several types of cancer. However, the potential function of FAM83H in pancreatic cancer (PC) still remain unknown.

Aim

This study aims to explore the role of FAM83H during pancreatic carcinogenesis and the regulation of immune infiltration in PC.

Methods

In the current study, the clinical significance and potential biological of FAM83H were evaluated by bioinformatics analysis. Possible associations between FAM83H expression and tumor immunity were analyzed using ESTIMATE algorithm and single-sample gene set enrichment analysis (ssGSEA).

Results

FAM83H expression was significantly upregulated in tumor tissues, and positively associated with higher histologic grade, tumor recurrence, and worse prognosis. FAM83H overexpression is notably associated with KRAS activation. And functional enrichment analysis demonstrated that FAM83H may be involved in positive regulation of cell proliferation and migration, Ras protein signal transduction, regulation of cell–matrix adhesion, epithelial to mesenchymal transition (EMT), TGF-β receptor signaling in EMT, and activated NOTCH transmits signal to the nucleus. ESTIMATE algorithm and ssGSEA demonstrated that FAM83H overexpression suppressed the infiltration and antitumor activity of tumor-infiltrating lymphocytes (TILs), especially for CD8+ T cells. Besides, FAM83H overexpression significantly correlated with low expression of TIL-related gene markers (e.g. CD8A, CD8B, CD2, CD3D, and CD3E).

Conclusion

The study suggests that FAM83H overexpression predicts poor prognosis and correlates with less CD8+ T cells infiltration and Ras-PI3K-Akt-mTOR signaling pathway in PC.

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Acknowledgements

This study was supported by National Natural Science Foundation of China (project NO.: 81702783 and 81672475) and Natural Science Foundation of Guangdong Province (project NO.: 2017A030310574).

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Authors and Affiliations

  1. Shantou University of Medical College, Shantou, 515000, China

    H. Zhuang

  2. Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou, 510080, China

    H. Zhuang, C. Zhang & B. Hou

Authors
  1. H. Zhuang
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  2. C. Zhang
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  3. B. Hou
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Contributions

Conceiving, H-KZ; data curation, H-KZ; funding acquisition, C-ZZ, B-HH; investigation, H-KZ; methodology, H-KZ; resources, C-ZZ, B-HH; validation, H-KZ, C-ZZ; visualization, H-KZ; writing—original draft, H-KZ.

Corresponding authors

Correspondence to C. Zhang or B. Hou.

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The authors declare that there is no conflict of interest.

Ethical standards

All datasets (TCGA, GSE62452, GSE60979, GSE28735, and GSE79668) are freely available as public resources. Therefore, local ethics approval was not needed.

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Zhuang, H., Zhang, C. & Hou, B. FAM83H overexpression predicts worse prognosis and correlates with less CD8+ T cells infiltration and Ras-PI3K-Akt-mTOR signaling pathway in pancreatic cancer. Clin Transl Oncol 22, 2244–2252 (2020). https://doi.org/10.1007/s12094-020-02365-z

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  • DOI: https://doi.org/10.1007/s12094-020-02365-z

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