Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
The Chemical Glycobiology Laboratory, The Francis Crick Institute, NW1 1AT, London, UK.
Oncogene. 2023 Mar;42(12):926-937. doi: 10.1038/s41388-023-02604-x. Epub 2023 Feb 1.
Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression.
前列腺癌是男性中最常见的癌症，据估计，全世界每年有超过 35 万名男性死于前列腺癌。目前仍存在临床需求，需要改善如何诊断具有临床意义的前列腺癌，并开发治疗晚期疾病的新方法。异常糖基化是癌症的一个标志，与肿瘤生长、转移和免疫逃逸有关。异常糖基化的一个关键驱动因素是癌症细胞内糖基化酶的失调表达。在这里，我们使用多个独立的临床队列证明，糖基转移酶酶 GALNT7 在前列腺癌组织中上调。我们表明，GALNT7 可以使用尿液和血液样本识别患有前列腺癌的男性，其诊断准确性优于单独的血清 PSA。我们还表明，GALNT7 水平在进展为去势抵抗性疾病时仍然很高，并且通过体外和体内模型揭示，GALNT7 促进前列腺肿瘤生长。在机制上，GALNT7 可以修饰前列腺癌细胞中的 O-糖基化，并与细胞周期和免疫信号通路相关。我们的研究提供了一种新的生物标志物来辅助具有临床意义的疾病的诊断，并确定 GALNT7 介导的 O-糖基化是前列腺癌进展的重要驱动因素。
