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 PIGY in these six cancers was increased. In addition, the expression of CD14, a GPI-AP gene, was increased in these six cancers. The expression of GAS1, GPC2 and GPC4 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.
人体细胞中含有超过146种GPI锚定蛋白(glycosylphosphatidylinositol-anchored protein, GPI-AP)，包括受体、配体、粘附分子和酶等。这些蛋白通过GPI锚定在细胞膜表面的脂筏中，发挥多种重要生物学功能。目前，已经对GPI锚定蛋白的生物合成开展了大量研究，其中GPI-AP的生物合成包括至少20步反应，已鉴定出超过40个GPI-AP合成相关基因，但是仍缺乏对于GPI-AP相关基因在正常组织与癌症组织中表达调控的研究。本研究利用来自于TCGA数据库和GTEx portal的基因表达数据，同时结合使用GlycoMaple糖基化通路分析工具，对正常组织与癌症组织中参与GPI-AP合成和编码GPI-AP的基因的表达情况进行了全面分析。研究发现，与正常组织相比，在早期胶质瘤、多形性胶质母细胞瘤、胰腺癌、睾丸生殖细胞癌、原发性皮肤黑色素瘤和转移性皮肤黑色素瘤中，参与GPI-AP合成的基因表达发生了显著变化，其中PIGY在这6种癌症中表达量均有上升。此外，GPI锚定蛋白编码基因CD14在这6种癌症中的表达量上升。GPI锚定蛋白编码基因GAS1、GPC2、GPC4仅在早期胶质瘤和多形性胶质母细胞瘤中表达量上升，说明部分GPI锚定蛋白如GAS1等可以作为早期胶质瘤和多形性胶质母细胞瘤生物标志物。本研究为GPI-AP相关基因在正常组织与癌症组织中的表达情况提供了新的见解，为GPI-AP作为生物标志物的开发打下了坚实基础。.
Keywords: Cancer; Glioma; Glycosylphosphatidylinositol anchored protein(GPI-AP); TCGA.