A multi-cancer analysis unveils ITGBL1 as a cancer prognostic molecule and a novel immunotherapy target

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-01-15 DOI:10.1515/oncologie-2023-0455

Ziyu Wu, Zhihong Liu, Changji Gu, Yong Wu, Yanan Li, Zeyang Zhou, Xiaodong Yang

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引用次数: 0

Abstract

Abstract Objectives Integrin subunit beta-like 1 (ITGBL1), a member of the epidermal growth factor (EGF)-like protein family, encodes a beta integrin-related protein that is mainly associated with the development of specific tumours and immune-related signalling pathways. This work aimed to explore the possibility that ITGBL1 functions as a novel target gene for immunotherapy and could be a cancer prognostic molecule. Methods The mRNA data for ITGBL1 were obtained from the public databases The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO). Using GEPIA, the differential expression of ITGBL1 in different tumour stages was identified. Cancer prognostic correlations were explored using Kaplan–Meier survival analysis and forest plots. A combination of Gene Set Enrichment Analysis (GSEA), TIMER2.0 and the R package was applied to analyse the ITGBL1-enriched related pathways. The NCI-60 drug database was examined using CellMinerTM. Cytological experiments were conducted to confirm ITGBL1’s impact on cancer cells. Results Our research has shown that ITGBL1 is differentially expressed in 26 cancers, and high ITGBL1 expression predicts a poorer survival prognosis in some specific cancers. Additionally, we found that ITGBL1 is enriched in immune-related pathways, which are closely linked to immunomodulatory molecules, immune-infiltrating cells, and immunomodulatory factors. The results of tumor mutational burden (TMB) and microsatellite instability (MSI) also indicate that the expression of ITGBL1 is beneficial for improving tumor immunotherapy efficacy. Furthermore, a number of antitumor agents associated with ITGBL1 expression have been identified. Finally, knockdown of ITGBL1 restricts the ability of gastric and colorectal cancer cells to proliferate and migrate. Conclusions Our study demonstrates that ITGBL1 can be utilized to accurately prognosticate cancer and has opened up new avenues for the investigation of tumor immune mechanisms and the development of more efficacious immunotherapies.

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多癌症分析揭示 ITGBL1 是癌症预后分子和新型免疫疗法靶点

摘要目的整合素亚基 beta-like 1（ITGBL1）是表皮生长因子（EGF）样蛋白家族的成员，它编码一种与 beta 整合素相关的蛋白，主要与特定肿瘤的发展和免疫相关的信号通路有关。本研究旨在探讨 ITGBL1 作为免疫疗法新靶基因的可能性，并探讨其作为癌症预后分子的可能性。方法 ITGBL1的mRNA数据来自公共数据库癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）和基因表达总库（GEO）。通过 GEPIA，确定了 ITGBL1 在不同肿瘤分期中的差异表达。利用卡普兰-米尔生存分析和森林图探讨了癌症预后的相关性。结合基因组富集分析（Gene Set Enrichment Analysis，GSEA）、TIMER2.0和R软件包分析了ITGBL1富集的相关通路。使用 CellMinerTM 检查了 NCI-60 药物数据库。细胞学实验证实了 ITGBL1 对癌细胞的影响。结果我们的研究表明，ITGBL1 在 26 种癌症中有不同程度的表达，ITGBL1 的高表达预示着某些特定癌症的生存预后较差。此外，我们还发现 ITGBL1 富集在免疫相关通路中，这些通路与免疫调节分子、免疫浸润细胞和免疫调节因子密切相关。肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）的研究结果也表明，ITGBL1的表达有利于提高肿瘤免疫治疗的疗效。此外，还发现了一些与 ITGBL1 表达相关的抗肿瘤药物。最后，敲除 ITGBL1 会限制胃癌和结直肠癌细胞的增殖和迁移能力。结论我们的研究表明，ITGBL1 可用于准确预测癌症预后，并为研究肿瘤免疫机制和开发更有效的免疫疗法开辟了新途径。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.