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4级弥漫性胶质瘤中血管生成相关基因的预后及免疫浸润分析

Prognosis and immunoinfiltration analysis of angiogene-related genes in grade 4 diffuse gliomas.

作者信息

Liu Hui, Zeng Zhirui, Sun Peng

机构信息

Department of Neurosurgery, Affiliated Hospital of Qingdao University, Qingdao, China.

Department of Neurosurgery, Guizhou Medical University, Guiyang, China.

出版信息

Aging (Albany NY). 2023 Sep 21;15(18):9842-9857. doi: 10.18632/aging.205054.

Abstract

Although angiogenesis critically influences the progression of solid tumors, its contribution to highly malignant, grade 4 diffuse gliomas remains unclear. After analyzing 506 angiogenesis-related genes differentially expressed in grade 4 diffuse gliomas via LASSO and univariate and multivariate COX regression analyses, we constructed a nomogram based on COL22A1, IGFBP2, and MPO that accurately predicted patient survival. The nomogram's performance was validated in an external patient cohort, and a risk score based on the formula COL22A10.148+IGFBP20.234+MPO*0.145 was used to distinguish high-risk from low-risk patients. Based on differentially expressed genes among risk groups, functional enrichment and drug sensitivity analyses were conducted, and the association between COL22A1, IGFBP2, and MPO expression and infiltrating immune cells and immune checkpoint genes was investigated. We next focused on COL22A1, and verified its overexpression in both glioma cell lines and clinical samples. A pro-oncogenic role for COL22A1, evidenced by impaired proliferation, migration, and invasion capacities, was evidenced upon shRNA-mediated COL22A1 silencing in glioma U87 and LN18 cells. In summary, we present a novel nomogram based on the angiogenesis-related genes COL22A1, IGFBP2, and MPO that allows survival prediction in patients with grade 4 diffuse gliomas. Furthermore, our cellular assays support a pro-oncogenic role for COL22A1 in these tumors.

摘要

尽管血管生成对实体瘤的进展具有关键影响,但其对高度恶性的4级弥漫性胶质瘤的作用仍不清楚。通过LASSO以及单变量和多变量COX回归分析,我们分析了4级弥漫性胶质瘤中506个差异表达的血管生成相关基因,基于COL22A1、IGFBP2和MPO构建了一个能准确预测患者生存的列线图。该列线图的性能在外部患者队列中得到验证,并使用基于公式COL22A10.148 + IGFBP20.234 + MPO*0.145的风险评分来区分高风险和低风险患者。基于风险组之间的差异表达基因,进行了功能富集和药物敏感性分析,并研究了COL22A1、IGFBP2和MPO表达与浸润免疫细胞和免疫检查点基因之间的关联。接下来我们聚焦于COL22A1,并在胶质瘤细胞系和临床样本中验证了其过表达。在胶质瘤U87和LN18细胞中,通过shRNA介导的COL22A1沉默,证实了COL22A1具有促癌作用,表现为增殖、迁移和侵袭能力受损。总之,我们提出了一种基于血管生成相关基因COL22A1、IGFBP2和MPO的新型列线图,可用于预测4级弥漫性胶质瘤患者的生存情况。此外,我们的细胞实验支持COL22A1在这些肿瘤中具有促癌作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ab1/10564429/3b990df16787/aging-15-205054-g001.jpg

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