关键词: Breast cancer GPS1 Immune cell infiltration Prognosis

Mesh : Female Humans Breast Breast Neoplasms / genetics Computational Biology COP9 Signalosome Complex / genetics Databases, Factual Trans-Activators Tumor Microenvironment

来  源:   DOI:10.1007/s00432-023-05569-2   PDF(Pubmed)

Abstract:
G protein pathway suppressor 1 (GPS1) is involved in the development of many diseases including tumors, but its specific regulatory mechanism in breast cancer is not clear. The goal of the present study was to explore the biological effects and underlying mechanism of GPS1 in breast cancer. Public databases were used to analyze GPS1 expression and the relationship with clinicopathological characteristics and prognosis of breast cancer patients, combined with in vitro experiments to analyze the mechanism of action and immune relevance of GPS1 in breast cancer. Data analysis showed that the expression of GPS1 in breast cancer tissues was significantly higher than that in paracancerous tissues (p < 0.001), and the receiver operating curve (ROC) revealed a higher diagnostic efficiency (AUC = 0.832). Survival analyses indicated that patients with high GPS1 expression made the prognosis worse in Luminal B, low to intermediate-grade breast cancers. Enrichment analysis showed that GPS1 was involved in the formation of ribonucleoprotein complexes, which dynamically altered the fate of RNA; it could also enhance the responsiveness of the Wnt pathway by interacting with WBP2. In addition, GPS1 expression was closely related to the immune microenvironment. GPS1 knockdown inhibits the proliferation, invasion and migration of MCF7 and MDA-MB-231 cells in vitro. This study suggests that the upregulation of GPS1 is associated with the malignant biological behavior and prognosis of breast cancer and may promote cancer progression. The correlation between GPS1 and the immune microenvironment suggests that it may be a potential target for immunotherapy.
摘要:
G蛋白通路抑制因子1(GPS1)参与包括肿瘤在内的多种疾病的发生发展,但其在乳腺癌中的具体调控机制尚不清楚。本研究的目的是探讨GPS1在乳腺癌中的生物学效应和潜在机制。应用公共数据库分析乳腺癌患者GPS1表达及其与临床病理特征和预后的关系。结合体外实验分析GPS1在乳腺癌中的作用机制及免疫相关性。数据分析显示GPS1在乳腺癌组织中的表达明显高于癌旁组织(p<0.001),受试者工作曲线(ROC)显示更高的诊断效率(AUC=0.832)。生存分析显示GPS1高表达患者LuminalB的预后更差,低到中级乳腺癌。富集分析表明GPS1参与核糖核蛋白复合物的形成,动态改变RNA的命运;它还可以通过与WBP2相互作用来增强Wnt途径的反应性。此外,GPS1的表达与免疫微环境密切相关。GPS1敲低抑制增殖,MCF7和MDA-MB-231细胞的体外侵袭和迁移。这项研究表明,GPS1的上调与乳腺癌的恶性生物学行为和预后有关,并可能促进癌症的进展。GPS1与免疫微环境之间的相关性表明它可能是免疫疗法的潜在靶标。
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