Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan-cancer analysis

IF 4.6 2区 医学 Q2 IMMUNOLOGY Clinical & Translational Immunology Pub Date : 2024-10-04 DOI:10.1002/cti2.70009
Yifan Liu, Yuntao Yao, Xinyue Yang, Maodong Wei, Bingnan Lu, Keqing Dong, Donghao Lyu, Yuanan Li, Wenbin Guan, Runzhi Huang, Guofeng Xu, Xiuwu Pan
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Abstract

Objectives

Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T-cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan-cancer scale. Thus, we aim to reveal its role at the pan-cancer level.

Methods

We performed IHC staining on a retrospective cohort of 370 patients. Then we assessed the prognostic effect of LAG3 using Kaplan–Meier survival analysis and multivariate Cox regression analysis. In pan-cancer analysis, we constructed competing endogenous RNA and protein–protein interaction networks, conducted gene set enrichment analysis and identified correlations between LAG3 gene expression and various factors, including clinical characteristics, tumour purity, mutations, tumour immunity and drug sensitivity across 33 cancer types.

Results

LAG3 was expressed higher in normal kidney tissues than in tumours. A high level of LAG3 gene expression was an independent prognostic factor for OS (HR = 6.60, 95% CI = 2.43–17.90, P < 0.001) and PFS (HR = 3.44, 95% CI = 1.68–7.10, P < 0.001). In pan-cancer analysis, LAG3 exhibited robust correlations with survival and tumour stages in various cancers. Moreover, LAG3 was strongly associated with immune-related genes, proteins and signalling pathways. LAG3 gene expression was positively associated with increased infiltration of activated immune cells and decreased infiltration of several resting cells. LAG3 gene expression was associated with tumour mutation burden and microsatellite instability in multiple cancers.

Conclusion

High LAG3 gene expression was an independent risk factor in kidney neoplasms. It also functioned as a biomarker for prognosis, TIME and immunotherapy efficacy in the pan-cancer dimension.

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淋巴细胞活化基因 3 是不同癌症类型的潜在预后和免疫生物标记物:一项临床和泛癌症分析。
研究目的淋巴细胞活化基因 3(LAG3)是 T 细胞活化过程中的一个抑制受体,是一个不利的预后因素。然而,它对肿瘤的影响尚未在泛癌症范围内得到全面阐明。因此,我们旨在揭示它在泛癌症中的作用:方法:我们对 370 例患者的回顾性队列进行了 IHC 染色。方法:我们对 370 例回顾性患者进行了 IHC 染色,然后使用 Kaplan-Meier 生存分析和多变量 Cox 回归分析评估了 LAG3 的预后作用。在泛癌症分析中,我们构建了竞争内源性RNA和蛋白-蛋白相互作用网络,进行了基因组富集分析,并确定了33种癌症类型中LAG3基因表达与临床特征、肿瘤纯度、突变、肿瘤免疫和药物敏感性等各种因素之间的相关性:结果:LAG3在正常肾组织中的表达高于肿瘤。LAG3基因高表达是OS的独立预后因素(HR = 6.60,95% CI = 2.43-17.90, P P 结论:LAG3基因高表达是OS的独立预后因素:LAG3基因高表达是肾脏肿瘤的一个独立危险因素。在泛癌症维度上,它还是预后、TIME和免疫疗法疗效的生物标志物。
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来源期刊
Clinical & Translational Immunology
Clinical & Translational Immunology Medicine-Immunology and Allergy
CiteScore
12.00
自引率
1.70%
发文量
77
审稿时长
13 weeks
期刊介绍: Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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