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Elevated GALNT10 expression identifies immunosuppressive microenvironment and dismal prognosis of patients with high grade serous ovarian cancer

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Abstract

High grade ovarian serous cancer (HGSC) is a malignant disease with high mortality. Glycosylation plays important roles in tumor invasion and immune evasion, but its effect on the immune microenvironment of HGSC remains unclear. This study examined the association of glycosyltransferase expression with HGSC prognosis and explored the underlying mechanism using clinical specimens and integrated bioinformatic analyses. We identified a cluster of 15 glycogenes associated with reduced overall survival, and GALNT10 was found to be an independent predictor of HGSC prognosis. The high GALNT10 expression was associated with increased regulatory CD4+ T cells infiltration and decreased granzyme B expression in CD8+ T cells. The expression of GALNT10 and its product, Tn antigen, in HGSC specimens was associated with the increased infiltration of M2 macrophages and neutrophils, and the decreased infiltration of CD3+ T cells, NK cells, and B cells. Taken collectively, high GALNT10 expression confers with immunosuppressive microenvironment to promote tumor progression and predicts poor clinical outcomes in HGSC patients.

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Abbreviations

CI:

Confidence interval

ES:

Enrichment scores

GEO:

Gene expression Omnibus

GSEA:

Gene set enrichment analysis

GZMB:

Granzyme B

HGSC:

High grade serous ovarian cancer

HR:

Hazard ratio

MUC:

Mucin

ST:

Sialyl-T

sTn:

Sialyl Tn

TAM:

Tumor-associated macrophages

TCGA:

The cancer genome atlas

VVA:

Vicia villosa agglutinin

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Funding

This work was supported by funding from the National Key R&D Program of China (2016YFC1303100), National Natural Science Foundation of China (31570803, 81773090), and Research Program of Shanghai Municipal Commission of Health and Family Planning (20154Y0049).

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Author notes

  1. Guodong Zhang, Jiaqi Lu, and Moran Yang have contributed equally to this article.

Authors and Affiliations

  1. Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China

    Guodong Zhang, Jiaqi Lu, Moran Yang, Yiying Wang, Haiou Liu & Congjian Xu

  2. Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, No. 128, Shenyang Road, Shanghai, 200011, China

    Guodong Zhang & Congjian Xu

  3. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, China

    Moran Yang, Yiying Wang, Haiou Liu & Congjian Xu

  4. Department of Gynecology, Kashgar Prefecture Second People’s Hospital, Kashi, Xinjiang, 844000, China

    Jiaqi Lu

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  1. Guodong Zhang
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  2. Jiaqi Lu
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  3. Moran Yang
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  4. Yiying Wang
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Contributions

HL designed and executed experiments and contributed to the revision of the manuscript. CX contributed to the design of the experiments and prepared the manuscript. GZ and MY performed IHC, IF, and flow cytometry experiments and analyzed the bioinformatics data. JL contributed to the analysis of the data and manuscript preparation. YW contributed to the analysis of the immune cell infiltration data.

Corresponding authors

Correspondence to Haiou Liu or Congjian Xu.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Obstetrics and Gynecology Hospital, Fudan University (Kyy2016-49, for cohort 1; Kyy2017-27, for cohort 3) and the Ethics Committee of Suzhou Municipal Hospital (2018-0715, for cohort 2).

Informed consent

All participants included in this study provided written informed consent, which allowed us to use their specimens and data for publication. In this study, patients in cohort 1 and 2 provided informed consent prior to surgery for the use of their paraffin-embedded tissue blocks after a definitive diagnosis, and patients in cohort 3 provided informed consent for use of fresh tissues before surgery.

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Zhang, G., Lu, J., Yang, M. et al. Elevated GALNT10 expression identifies immunosuppressive microenvironment and dismal prognosis of patients with high grade serous ovarian cancer. Cancer Immunol Immunother 69, 175–187 (2020). https://doi.org/10.1007/s00262-019-02454-1

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