Integrin subunit alpha V is a potent prognostic biomarker associated with immune infiltration in lower-grade glioma

Zilong Tan; Zhe Zhang; Kai Yu; Huan Yang; Huaizhen Liang; Tianzhu Lu; Yulong Ji; Junjun Chen; Wei He; Zhen Chen; Yuran Mei; Xiao-Li Shen

doi:10.3389/fneur.2022.964590

Integrin subunit alpha V is a potent prognostic biomarker associated with immune infiltration in lower-grade glioma

Front Neurol. 2022 Oct 25:13:964590. doi: 10.3389/fneur.2022.964590. eCollection 2022.

Authors

Zilong Tan^{1

2

3}, Zhe Zhang^{1

2

3}, Kai Yu⁴, Huan Yang⁵, Huaizhen Liang⁶, Tianzhu Lu⁷, Yulong Ji², Junjun Chen², Wei He¹, Zhen Chen¹, Yuran Mei¹, Xiao-Li Shen^{1

2}

Affiliations

¹ Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
² Jiangxi Key Laboratory of Translational Cancer Research, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China.
³ The Graduate Department, Jiangxi Medical College of Nanchang University Nanchang, Nanchang, China.
⁴ Department of Neurosurgery, People's Hospital of Wuhan University, Wuhan, China.
⁵ Department of Neurosurgery, Changde Hospital of Traditional Chinese Medicine, Changde, China.
⁶ Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁷ Department of Radiation Oncology, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China.

Abstract

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 (n = 528) and the Chinese Glioma Genome Atlas dataset (n = 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 via immunohistochemistry (IHC). ITGAV expression was higher in LGG tissues than in normal tissues (P < 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, P < 0.001). GSEA showed that ITGAV expression was correlated with Inflammatory response, complement response, KRAS 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.

Keywords: biological function; biomarker; integrin subunit alpha V; low grade glioma; prognosis.