Zhan Lu, Zeng Fanyue, Zheng Jie, Chen Sijing, Zhang Zhiyun, Ju Donghui
Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Cancer Biomark. 2025 Mar;42(3):18758592251328162. doi: 10.1177/18758592251328162. Epub 2025 Apr 2.
BackgroundCanopy FGF signalling regulator 3 (CNPY3) is involved in immune regulation, tumorigenesis and development, nevertheless, its role in glioma remains largely unexplored. Our study aimed to explore the regulatory role of CNPY3 as a prognostic biomarker in human glioma cell migration, invasion and immune infiltration.MethodsBioinformatics analysis of CNPY3 and clinical relevance of glioma in public databases was performed. COX regression analysis was performed to assess the relationship between CNPY3 and glioma prognosis. GO and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to predict the signaling pathways of CNPY3 in gliomas. Tumor immune infiltration was explored using TIMER, CIBERSORT, and Pearson correlation analysis. GSVA analysis and single-cell sequencing data were employed for further validation. The effects of CNPY3 on the migration and invasion of glioma cells were investigated through cell scratch assay and transwell assay.ResultsCNPY3 was positively correlated with IDH mutation status, 1p/19q status, histopathologic grade, and MGMT promoter methylation status, but negatively with the overall survival of glioma patients (< 0.05). CNPY3 was significantly associated with tumor immune response, inflammatory response, and lipopolysaccharide-mediated signaling pathway. CNPY3 influenced different types of immune cells which affected the immune microenvironment of glioma. CNPY3 promoted the increase of M2 macrophage and was negatively correlated with the positive regulation of macrophages apoptotic process. In vitro data suggested the promotion of CNPY3 in U87MG cells was associated with an increased capacity for cell migration and invasion (< 0.05). Tumor drug sensitivity analysis showed more sensitivity towards temozolomide, irinotecan, and cisplatin among high CNPY3 expression patients (< 0.05).ConclusionIncreased CNPY3 expression impacts the immune microenvironment of glioma and enhances the migration and invasion of glioma. CNPY3 is recommended as a prognostic biomarker for glioma patients.
背景
冠层成纤维细胞生长因子信号调节因子3（CNPY3）参与免疫调节、肿瘤发生和发展，然而，其在胶质瘤中的作用在很大程度上仍未被探索。我们的研究旨在探讨CNPY3作为一种预后生物标志物在人类胶质瘤细胞迁移、侵袭和免疫浸润中的调节作用。
方法
对公共数据库中CNPY3和胶质瘤的临床相关性进行生物信息学分析。进行COX回归分析以评估CNPY3与胶质瘤预后之间的关系。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析以预测CNPY3在胶质瘤中的信号通路。使用TIMER、CIBERSORT和Pearson相关分析探索肿瘤免疫浸润。采用基因集变异分析（GSVA）和单细胞测序数据进行进一步验证。通过细胞划痕试验和Transwell试验研究CNPY3对胶质瘤细胞迁移和侵袭的影响。
结果
CNPY3与异柠檬酸脱氢酶（IDH）突变状态、1p/19q状态、组织病理学分级和O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化状态呈正相关，但与胶质瘤患者的总生存期呈负相关（<0.05）。CNPY3与肿瘤免疫反应、炎症反应和脂多糖介导的信号通路显著相关。CNPY3影响不同类型的免疫细胞，进而影响胶质瘤的免疫微环境。CNPY3促进M2巨噬细胞增加，与巨噬细胞凋亡过程的正调控呈负相关。体外数据表明，CNPY3对U87MG细胞的促进作用与细胞迁移和侵袭能力增加有关（<0.05）。肿瘤药物敏感性分析显示，CNPY3高表达患者对替莫唑胺、伊立替康和顺铂更敏感（<0.05）。
结论
CNPY3表达增加影响胶质瘤的免疫微环境，增强胶质瘤的迁移和侵袭。建议将CNPY3作为胶质瘤患者的预后生物标志物。
