Glypican-3 (GPC3) 是一种膜结合硫酸乙酰肝素蛋白聚糖，长期以来被发现在人肺腺癌 (LUAD) 中失调。然而，GPC3 基因在 LUAD 进展中的功能、突变谱、表观遗传调控、共表达谱和临床病理学意义尚不清楚。在本研究中，我们使用生物信息学工具分析了公共数据库中的癌症微阵列数据集，以阐明上述参数。我们观察到，与正常组织相比，LUAD 组织中 GPC3 显着下调，这种下调与较短的总生存期 (OS) 和无复发生存期 (RFS) 相关。然而，尽管在男性患者中观察到较低的启动子甲基化，但在 LUAD 和正常组织之间没有观察到 GPC3 甲基化模式的显着差异。还发现 GPC3 表达与 LUAD 中 B 细胞、CD8、CD4、巨噬细胞、中性粒细胞和树突状细胞的浸润显着相关。此外，在 LUAD 患者中总共鉴定出 11 个错义突变，大约 1.4% 至 2.2% 的 LUAD 患者在 GPC3 中存在拷贝数扩增。 17 个基因，主要涉及多巴胺受体介导的信号通路，经常与 GPC3 共表达。我们还发现 11 个 TF 和 7 个 miRNA 与 GPC3 相互作用并促进疾病进展。最后，我们确定了人 LUAD 中 3 种潜在的 GPC3 抑制剂，即肝素、吉西他滨和熊果苷。总之，GPC3 可能在 LUAD 的发展中发挥重要作用，并可以作为 LUAD 中一个有前途的生物标志物。版权所有 © 2023 作者。由 Wolters Kluwer Health, Inc. 出版

Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has long been found to be dysregulated in human lung adenocarcinomas (LUADs). Nevertheless, the function, mutational profile, epigenetic regulation, co-expression profile, and clinicopathological significance of the GPC3 gene in LUAD progression are not well understood. In this study, we analyzed cancer microarray datasets from publicly available databases using bioinformatics tools to elucidate the above parameters. We observed significant downregulation of GPC3 in LUAD tissues compared to their normal counterparts, and this downregulation was associated with shorter overall survival (OS) and relapse-free survival (RFS). Nevertheless, no significant differences in the methylation pattern of GPC3 were observed between LUAD and normal tissues, although lower promoter methylation was observed in male patients. GPC3 expression was also found to correlate significantly with infiltration of B cells, CD8+, CD4+, macrophages, neutrophils, and dendritic cells in LUAD. In addition, a total of 11 missense mutations were identified in LUAD patients, and ~1.4% to 2.2% of LUAD patients had copy number amplifications in GPC3. Seventeen genes, mainly involved in dopamine receptor-mediated signaling pathways, were frequently co-expressed with GPC3. We also found 11 TFs and 7 miRNAs interacting with GPC3 and contributing to disease progression. Finally, we identified 3 potential inhibitors of GPC3 in human LUAD, namely heparitin, gemcitabine and arbutin. In conclusion, GPC3 may play an important role in the development of LUAD and could serve as a promising biomarker in LUAD.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.