Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China.
Aging (Albany NY). 2021 Aug 30;13(16):20836-20852. doi: 10.18632/aging.203489.
Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate, regulates a variety of biological processes that promote tumor progression. In this study, we analyzed the correlation between HPSE expression and prognosis in cancer patients, using multiple databases (Oncomine, TIMER, PrognoScan, GEPIA, Kaplan-Meier plotter, miner v4.1, DAVID). HPSE expression was significantly increased in bladder, breast, lung, and stomach cancer compared to matched normal tissues. The increased HPSE expression correlated with poor prognosis and increased immune infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils and dendritic cells in bladder and breast cancer. In breast cancer, the high HPSE expression was associated with basal-like subtypes, younger age (0-40), advanced Scarff-Bloom-Richardson grade, Nottingham Prognostic Index and p53 mutation status. In addition, using a mouse model of breast cancer, our data showed that HPSE upregulated IL-10 expression and promoted macrophage M2 polarization and T cell exhaustion. Together, our data provide a novel immunological perspective on the mechanisms underlying breast cancer progression, and indicate that HPSE may serve as a biomarker for immune infiltration and prognosis in breast cancer.
肝素酶 (HPSE) 是一种能够切割肝素硫酸盐的内切糖苷酶，它调节着多种促进肿瘤进展的生物学过程。在这项研究中，我们使用多个数据库（Oncomine、TIMER、PrognoScan、GEPIA、Kaplan-Meier plotter、miner v4.1、DAVID）分析了 HPSE 表达与癌症患者预后之间的相关性。与配对的正常组织相比，膀胱癌、乳腺癌、肺癌和胃癌中 HPSE 的表达显著增加。HPSE 表达的增加与预后不良以及膀胱癌和乳腺癌中 B 细胞、CD8+和 CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞浸润水平的增加相关。在乳腺癌中，高 HPSE 表达与基底样亚型、年轻（0-40 岁）、高级 Scarff-Bloom-Richardson 分级、诺丁汉预后指数和 p53 突变状态有关。此外，使用乳腺癌小鼠模型，我们的数据表明 HPSE 上调了 IL-10 的表达，促进了巨噬细胞 M2 极化和 T 细胞耗竭。总之，我们的数据为乳腺癌进展的机制提供了一个新的免疫学视角，并表明 HPSE 可能作为乳腺癌免疫浸润和预后的标志物。
