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整合素α5是一种新型致癌生物标志物,与胶质瘤的肿瘤免疫微环境相关。

ITGA5 Is a Novel Oncogenic Biomarker and Correlates With Tumor Immune Microenvironment in Gliomas.

作者信息

Li Shuyu, Zhang Nan, Liu Shiyang, Zhang Hao, Liu Jiajing, Qi Yiwei, Zhang Qi, Li Xingrui

机构信息

Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

One-Third Lab, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

出版信息

Front Oncol. 2022 Mar 18;12:844144. doi: 10.3389/fonc.2022.844144. eCollection 2022.

Abstract

Gliomas are the most aggressive primary intracranial malignancies with poor overall survival. ITGA5 is one member of the integrin adhesion molecule family and is implicated in cancer metastasis and oncogenesis. However, few studies have explored the association between tumor immune microenvironment and ITGA5 expression level in gliomas. Firstly, we analyzed 3,047 glioma patient samples collected from the TCGA, the CGGA, and the GEO databases, proving that high ITGA5 expression positively related to aggressive clinicopathological features and poor survival in glioma patients. Then, based on the ITGA5 level, immunological characteristics and genomic alteration were explored through multiple algorithms. We observed that ITGA5 was involved in pivotal oncological pathways, immune-related processes, and distinct typical genomic alterations in gliomas. Notably, ITGA5 was found to engage in remolding glioma immune infiltration and immune microenvironment, manifested by higher immune cell infiltration when ITGA5 is highly expressed. We also demonstrated a strong correlation between ITGA5 and immune checkpoint molecules that may be beneficial from immune checkpoint blockade strategies. In addition, ITGA5 was found to be a robust and sensitive indicator for plenty of chemotherapy drugs through drug sensitivity prediction. Altogether, our comprehensive analyses deciphered the prognostic, immunological, and therapeutic value of ITGA5 in glioma, thus improving individual and precise therapy for combating gliomas.

摘要

神经胶质瘤是最具侵袭性的原发性颅内恶性肿瘤,总体生存率较低。整合素α5(ITGA5)是整合素粘附分子家族的成员之一,与癌症转移和肿瘤发生有关。然而,很少有研究探讨神经胶质瘤中肿瘤免疫微环境与ITGA5表达水平之间的关联。首先,我们分析了从TCGA、CGGA和GEO数据库收集的3047例神经胶质瘤患者样本,证明ITGA5高表达与神经胶质瘤患者侵袭性临床病理特征和较差的生存率呈正相关。然后,基于ITGA5水平,通过多种算法探索免疫特征和基因组改变。我们观察到ITGA5参与了神经胶质瘤的关键肿瘤发生途径、免疫相关过程和独特的典型基因组改变。值得注意的是,发现ITGA5参与重塑神经胶质瘤免疫浸润和免疫微环境,表现为ITGA5高表达时免疫细胞浸润增加。我们还证明了ITGA5与免疫检查点分子之间存在强相关性,这可能从免疫检查点阻断策略中受益。此外,通过药物敏感性预测发现ITGA5是多种化疗药物的强大且敏感的指标。总之,我们的综合分析解读了ITGA5在神经胶质瘤中的预后、免疫和治疗价值,从而改善了对抗神经胶质瘤的个体化和精准治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fccb/8971292/d4cae1b065bd/fonc-12-844144-g001.jpg

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