Tan Zilong, Zhang Zhe, Yu Kai, Yang Huan, Liang Huaizhen, Lu Tianzhu, Ji Yulong, Chen Junjun, He Wei, Chen Zhen, Mei Yuran, Shen Xiao-Li
Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Key Laboratory of Translational Cancer Research, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China.
Front Neurol. 2022 Oct 25;13:964590. doi: 10.3389/fneur.2022.964590. eCollection 2022.
As a member of integrin receptor family, ITGAV (integrin subunit α V) is involved in a variety of cell biological processes and overexpressed in various cancers, which may be a potential prognostic factor. However, its prognostic value and potential function in lower-grade glioma (LGG) are still unclear, and in terms of immune infiltration, it has not been fully elucidated. Here, the expression preference, prognostic value, and clinical traits of ITGAV were investigated using The Cancer Genome Atlas database ( = 528) and the Chinese Glioma Genome Atlas dataset ( = 458). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA) were used to explore the biological function of ITGAV. Using R package "ssGSEA" analysis, it was found thatthe ITGAV mRNA expression level showed intense correlation with tumor immunity, such as tumor-infiltrating immune cells and multiple immune-related genes. In addition, ITGAV is associated with some immune checkpoints and immune checkpoint blockade (ICB) and response to chemotherapy. and the expression of ITGAV protein in LGG patients was verified immunohistochemistry (IHC). ITGAV expression was higher in LGG tissues than in normal tissues ( < 0.001) and multifactor analysis showed that ITGAV mRNA expression was an independent prognostic factor for LGG overall survival (OS; hazard ratio = 2.113, 95% confidence interval = 1.393-3.204, < 0.001). GSEA showed that ITGAV expression was correlated with Inflammatory response, complement response, signal, and interferon response. ssGSEA results showed a positive correlation between ITGAV expression and Th2 cell infiltration level. ITGAV mRNA was overexpressed in LGG, and high ITGAV mRNA levels were found to be associated with poor protein expression and poor OS. ITGAV is therefore a potential biomarker for the diagnosis and prognosis of LGG and may be a potential immunotherapy target.
作为整合素受体家族的一员，ITGAV（整合素αV亚基）参与多种细胞生物学过程，且在多种癌症中过表达，这可能是一个潜在的预后因素。然而，其在低级别胶质瘤（LGG）中的预后价值和潜在功能仍不清楚，在免疫浸润方面也尚未完全阐明。在此，利用癌症基因组图谱数据库（n = 528）和中国胶质瘤基因组图谱数据集（n = 458）研究了ITGAV的表达偏好、预后价值和临床特征。采用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析以及基因集富集分析（GSEA）来探索ITGAV的生物学功能。使用R包“ssGSEA”分析发现，ITGAV mRNA表达水平与肿瘤免疫密切相关，如肿瘤浸润免疫细胞和多个免疫相关基因。此外，ITGAV与一些免疫检查点、免疫检查点阻断（ICB）及化疗反应相关。通过免疫组织化学（IHC）验证了LGG患者中ITGAV蛋白的表达。LGG组织中ITGAV表达高于正常组织（P < 0.001），多因素分析表明ITGAV mRNA表达是LGG总生存期（OS）的独立预后因素（风险比 = 2.113，95%置信区间 = 1.393 - 3.204，P < 0.001）。GSEA显示ITGAV表达与炎症反应、补体反应、信号和干扰素反应相关。ssGSEA结果显示ITGAV表达与Th2细胞浸润水平呈正相关。ITGAV mRNA在LGG中过表达，且发现高ITGAV mRNA水平与蛋白表达不良和OS不良相关。因此，ITGAV是LGG诊断和预后的潜在生物标志物，可能是潜在的免疫治疗靶点。
