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The expression of O-linked glycosyltransferase GALNT7 in breast cancer is dependent on estrogen-, progesterone-, and HER2-receptor status, with prognostic implications

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Abstract

GALNT7 is a glycosyltransferase enzyme transferring N-acetylgalactosamine to initiate O-linked glycosylation in the Golgi apparatus. Breast cancer is the most common cancer in women globally. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2; ERBB2) are important biomarkers in the prognosis and molecular subtyping of breast cancer. Here, we showed that ER-positive, PR-positive or HER2-positive breast tumors have higher expression of GALNT7 compared to ER-negative, PR-negative or HER2-negative breast tumors, respectively. We found that CpG-aggregated methylation of GALNT7 gene is decreased, and in parallel, its transcript levels are increased in breast cancer compared to healthy breast tissue. We observed that the difference in the expression of GALNT7 between negative and positive status of the receptors is the highest for HER2, followed by ER and PR, pointing that HER2 might be relatively more influential than ER and PR on the expression of GALNT7 in breast cancer. We reported that basal-like breast tumors have decreased expression of GALNT7 compared to non-basal-like tumors, and that high GALNT7 expression is associated with favorable relapse-free and distant metastasis-free survival in HER2 status-dependent manner in breast cancer patients. Moreover, we showed that GALNT7 expression in breast cancer is cell type- (epithelial vs stromal cells), tumor grade- and ethnicity-dependent. Combined, we propose that GALNT7 might contribute to different clinical outcomes depending on the receptor status in breast cancer, and that a better understanding of GALNT7 and its function in the context of breast cancer is needed.

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Funding

CB is funded by TUBITAK (The Scientific and Technological Research Council of Turkey) 2211-E and 1001 programs. EC is funded by TUBITAK 1001 program.

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  1. Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, Tokat, Turkey

    Caglar Berkel & Ercan Cacan

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  1. Caglar Berkel
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CB: Conceptualization, Formal analysis, Investigation, Writing – original draft preparation, Visualization. EC: Resources, Writing – review and editing, Funding acquisition, Project administration, Supervision.

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Correspondence to Caglar Berkel.

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10719_2023_10137_MOESM1_ESM.pdf

Supplementary Fig. 1 Comparison of the expression of other polypeptide N-acetylgalactosaminyltransferases between non-malignant (normal) breast tissues and breast tumors. Data was obtained from TGCA. ns: p > 0.05; *: p <= 0.05; **: p <= 0.01; ***: p <= 0.001; ****: p<= 0.0001. (PDF 28 KB)

10719_2023_10137_MOESM2_ESM.pdf

Supplementary Fig. 2 The changes in the expression of mucin gene family between breast tumors and normal breast tissue. Data was obtained from TGCA. ns: p > 0.05; *: p <= 0.05; **: p <= 0.01; ***: p <= 0.001; ****: p <= 0.0001. (PDF 32 KB)

10719_2023_10137_MOESM3_ESM.pdf

Supplementary Fig. 3 Protein expression levels of GALNT7 in different cancer types. Data was obtained from Human Protein Atlas (proteinatlas.org). Antibody staining with two different antibodies against GALNT7, namely HPA064243 (bottom) and HPA065317 (top). (PDF 51 KB)

10719_2023_10137_MOESM4_ESM.png

Supplementary Fig. 4 A representative antibody staining image for GALNT7 in breast cancer. The image was obtained from Human Protein Atlas (proteinatlas.org). (PNG 580 KB)

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Berkel, C., Cacan, E. The expression of O-linked glycosyltransferase GALNT7 in breast cancer is dependent on estrogen-, progesterone-, and HER2-receptor status, with prognostic implications. Glycoconj J 40, 631–644 (2023). https://doi.org/10.1007/s10719-023-10137-4

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