Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, No. 128, Shenyang Road, Shanghai, 200011, China.
Cancer Immunol Immunother. 2020 Feb;69(2):175-187. doi: 10.1007/s00262-019-02454-1. Epub 2019 Dec 18.
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.
高级别卵巢浆液性癌(HGSC)是一种死亡率很高的恶性疾病。糖基化在肿瘤侵袭和免疫逃逸中起着重要作用,但它对 HGSC 免疫微环境的影响尚不清楚。本研究使用临床标本和综合生物信息学分析,研究了糖苷转移酶表达与 HGSC 预后的关系,并探讨了其潜在机制。我们确定了与总生存期缩短相关的 15 个糖基化基因簇,并且发现 GALNT10 是 HGSC 预后的独立预测因子。高 GALNT10 表达与调节性 CD4+T 细胞浸润增加和 CD8+T 细胞中颗粒酶 B 表达降低有关。HGSC 标本中 GALNT10 及其产物 Tn 抗原的表达与 M2 巨噬细胞和中性粒细胞浸润增加以及 CD3+T 细胞、NK 细胞和 B 细胞浸润减少有关。综上所述,高 GALNT10 表达赋予免疫抑制微环境,促进肿瘤进展,并预测 HGSC 患者的临床预后不良。