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确定整合素α3亚基(ITGA3)在人类癌症中的预后意义、免疫治疗反应预测价值及潜在的靶向化合物抑制剂。

Identifying the prognosis implication, immunotherapy response prediction value, and potential targeted compound inhibitors of integrin subunit α3 (ITGA3) in human cancers.

作者信息

Gui Jiawei, Yang Lufei, Liu Junzhe, Li Yishuang, Zou Mi, Sun Chengpeng, Huang Le, Zhu Xingen, Huang Kai

机构信息

Department of Neurosurgery, The 2 Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China.

HuanKui Academy, Jiangxi Medical College, Nanchang University, Nanchang 330031, PR China.

出版信息

Heliyon. 2024 Jan 6;10(2):e24236. doi: 10.1016/j.heliyon.2024.e24236. eCollection 2024 Jan 30.

Abstract

The integrin subunit α3 (ITGA3) is a member of the integrin alpha chain protein family, which could promote progression, metastasis, and invasion in some cancers. Still, its function in the tumor microenvironment (TME), cancer prognosis, and immunotherapy remains unclear. A multifaceted analysis of ITGA3 in pan-cancer utilizing various databases and online web tools revealed ITGA3 was aberrantly expressed in tumor tissues and upregulated in most cancers, which may be related to ITGA3 genomic alterations and methylation modification. In addition, ITGA3 was significantly correlated with the poor or better prognosis of cancer patients, immune-related pathways in hallmark, immune infiltration, and immune checkpoints, revealing a biological function of ITGA3 in the tumor progression, tumor microenvironment, and tumor immunity. We also found that ITGA3 could predict the response to tumor immunotherapy based on cytokine-treated samples and immunotherapy cohorts. ITGA3 may participate in shaping and regulating the tumor microenvironment to affect the tumor immune response, which was a promising immunotherapy response predictive biomarker and potential therapeutic target to work synergistically with cancer immunotherapy to boost the response and efficacy. Finally, potential targeted compound inhibitors and sensitive drugs were screened using databases ConnectivityMap (CMap) and CellMiner, and AutoDock Tools was used for molecular docking.

摘要

整合素亚基α3(ITGA3)是整合素α链蛋白家族的成员,它可促进某些癌症的进展、转移和侵袭。然而,其在肿瘤微环境(TME)、癌症预后和免疫治疗中的作用仍不清楚。利用各种数据库和在线网络工具对泛癌中的ITGA3进行多方面分析发现,ITGA3在肿瘤组织中异常表达,且在大多数癌症中上调,这可能与ITGA3的基因组改变和甲基化修饰有关。此外,ITGA3与癌症患者的预后不良或较好、标志性免疫相关途径、免疫浸润和免疫检查点显著相关,揭示了ITGA3在肿瘤进展、肿瘤微环境和肿瘤免疫中的生物学功能。我们还发现,基于细胞因子处理的样本和免疫治疗队列,ITGA3可以预测肿瘤免疫治疗的反应。ITGA3可能参与塑造和调节肿瘤微环境以影响肿瘤免疫反应,这是一种有前景的免疫治疗反应预测生物标志物和潜在治疗靶点,可与癌症免疫治疗协同作用以增强反应和疗效。最后,使用连通性图谱(CMap)和CellMiner数据库筛选了潜在的靶向化合物抑制剂和敏感药物,并使用自动对接工具进行分子对接。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2af4/10825359/e5228d8f4b82/gr1.jpg

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