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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
Glycoconjugate Journal ( IF 3 ) Pub Date : 2023-11-10 , DOI: 10.1007/s10719-023-10137-4
Caglar Berkel 1 , Ercan Cacan 1
Affiliation  

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.



中文翻译:

乳腺癌中 O 连接糖基转移酶 GALNT7 的表达依赖于雌激素、孕激素和 HER2 受体状态,具有预后意义

GALNT7 是一种糖基转移酶,可转移 N-乙酰半乳糖胺以启动高尔基体中的 O-连接糖基化。乳腺癌是全球女性最常见的癌症。雌激素受体 (ER)、孕激素受体 (PR) 和人表皮生长因子受体 2 (HER2; ERBB2) 是乳腺癌预后和分子分型的重要生物标志物。在这里,我们发现,与 ER 阴性、PR 阴性或 HER2 阴性乳腺肿瘤相比,ER 阳性、PR 阳性或 HER2 阳性乳腺肿瘤分别具有更高的 GALNT7 表达。我们发现,与健康乳腺组织相比,乳腺癌中 GALNT7 基因的 CpG 聚集甲基化降低,同时其转录水平升高。我们观察到受体阴性和阳性状态下 GALNT7 表达差异最大的是 HER2,其次是 ER 和 PR,这表明 HER2 对乳腺癌中 GALNT7 表达的影响可能相对大于 ER 和 PR 。我们报道,与非基底样肿瘤相比,基底样乳腺肿瘤的 GALNT7 表达降低,并且高 GALNT7 表达与乳腺癌患者 HER2 状态依赖性方式的良好无复发和无远处转移生存相关。此外,我们发现乳腺癌中的 GALNT7 表达与细胞类型(上皮细胞与基质细胞)、肿瘤分级和种族相关。综上所述,我们提出,根据乳腺癌中的受体状态,GALNT7 可能会导致不同的临床结果,并且需要更好地了解 GALNT7 及其在乳腺癌中的功能。

更新日期:2023-11-11
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