Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Yi Chuan. 2023 Aug 20;45(8):669-683. doi: 10.16288/j.yczz.23-043.
In human cells, there are more than 146 glycosylphosphatidylinositol-anchored proteins (GPI-APs), including receptors, ligands, adhesion molecules and enzymes. The proteins are associated with membrane microdomains called lipid rafts through GPI, and plays a variety of important biological functions. At present, plenty of studies have been carried out on the biosynthesis of GPI-APs. The biosynthesis of GPI-APs requires at least 20 steps, and more than 40 GPI biosynthetic genes have been identified. However, it remains unclear how expression of GPI-AP related genes is regulated in normal and cancer tissues. In this study, we utilized gene expression data from both the TCGA database and GTEx portal to analysis the gene expression involved in GPI-AP biosynthesis and encoding GPI-APs in normal and cancer tissues. In order to perform a comprehensive analysis, we employed the GlycoMaple, a tool that is specifically designed to analyze glycosylation pathways. The results showed that compared with normal tissues, the expression of genes involved in GPI-AP biosynthesis in cancer tissues such as early glioma, glioblastoma multiforme, pancreatic cancer, testicular germ cell carcinoma, skin primary cutaneous melanoma and skin metastatic cutaneous melanoma, was changed significantly. Particularly, the expression of in these six cancers was increased. In addition, the expression of , a GPI-AP gene, was increased in these six cancers. The expression of , and was increased only in early glioma and glioblastoma multiforme indicating that some GPI-APs such as GAS1 can be used as biomarkers of glioma. This study provides new insights into the expression of GPI-AP related genes in normal and cancer tissues, and lays a solid foundation for the development of GPI-APs as biomarkers.
在人类细胞中,有超过 146 种糖基磷脂酰肌醇锚定蛋白(GPI-APs),包括受体、配体、黏附分子和酶。这些蛋白质通过 GPI 与膜微区(称为脂筏)相关联,并发挥着各种重要的生物学功能。目前,已经有大量关于 GPI-AP 生物合成的研究。GPI-AP 的生物合成至少需要 20 步,已经鉴定出超过 40 个 GPI 生物合成基因。然而,GPI-AP 相关基因在正常组织和肿瘤组织中的表达调控机制仍不清楚。在这项研究中,我们利用 TCGA 数据库和 GTEx 门户中的基因表达数据,分析了 GPI-AP 生物合成和编码 GPI-APs 的基因在正常和肿瘤组织中的表达。为了进行全面分析,我们使用了 GlycoMaple,这是一种专门用于分析糖基化途径的工具。结果表明,与正常组织相比,早期神经胶质瘤、多形性胶质母细胞瘤、胰腺癌、睾丸生殖细胞癌、皮肤原发性黑色素瘤和皮肤转移性黑色素瘤等肿瘤组织中参与 GPI-AP 生物合成的基因表达发生了显著变化。特别是在这六种癌症中,基因的表达显著上调。此外,六种癌症中 GPI-AP 基因的表达也增加了。基因的表达在早期神经胶质瘤和多形性胶质母细胞瘤中上调,而基因的表达仅在早期神经胶质瘤和多形性胶质母细胞瘤中上调,这表明某些 GPI-APs,如 GAS1,可以作为神经胶质瘤的生物标志物。本研究为 GPI-AP 相关基因在正常和肿瘤组织中的表达提供了新的见解,并为 GPI-AP 作为生物标志物的开发奠定了基础。