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

Q: What is the main objective of this study regarding LAG3?

To clarify the role of LAG3 at a pan-cancer level by examining its prognostic significance and immunological associations across many cancer types.

Q: How was LAG3 prognostic impact evaluated in the clinical cohort?

Through immunohistochemistry in a retrospective cohort of 370 patients, followed by Kaplan–Meier survival analysis and multivariate Cox regression.

Q: What did pan-cancer analyses reveal about LAG3 and tumor biology?

LAG3 showed robust correlations with survival and tumor stages, strong links with immune-related genes and pathways, associations with immune cell infiltration patterns, and relationships with tumor mutation burden and microsatellite instability.

Sep 21, 2026

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Objectives. Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T-cell activation, is a negative prognostic factor, yet its impact on tumors has not been fully clarified across cancers. Methods. A retrospective cohort of 370 patients underwent immunohistochemistry, with prognostic assessment using Kaplan–Meier and multivariate Cox regression. Pan-cancer analyses built competing endogenous RNA and protein–protein interaction networks, applied gene set enrichment, and evaluated LAG3 links with clinical features, purity, mutations, immunity, and drug sensitivity across 33 cancer types. Results showed higher LAG3 in normal kidney than tumors, and high expression as an independent marker for OS and PFS, plus strong associations with immune biology, stage, TMB, and MSI; conclusions highlight LAG3 as a risk and biomarker across pan-cancer for prognosis, TIME, and immunotherapy efficacy.

LanguageEnglish

CategoryResearch & Report

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Pages20

Reading Time50 min

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Abstract

Introduction

Results

IHC staining and clinical correlation analyses with Xinhua cohort

Clinical & Translational Immunology 2024; 13: e70009 . doi: 10.1002/cti2.70009 [www.wileyonlinelibrary.com/journal/cti](www.wileyonlinelibrary.com/journal/cti) ORIGINAL ARTICLE Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan-cancer analysis Yifan Liu 1,a, Yuntao Yao 1,a, Xinyue Yang 1,a, Maodong Wei 1,a, Bingnan Lu 1,a, Keqing Dong 1, Donghao Lyu 1, Yuanan Li 1, Wenbin Guan2, Runzhi Huang3, Guofeng Xu 1 & Xiuwu Pan 1 1Department of Urology, Xinhua Hospital Afﬁliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China 2Department of Pathology, Xinhua Hospital Afﬁliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China 3Department of Burn Surgery, The First Afﬁliated Hospital of Naval Medical University, Shanghai, China Correspondence W Guan, Department of Pathology, Xinhua Hospital Afﬁliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. E-mail: [celiceli02@126.com](celiceli02@126.com) R Huang, Department of Burn Surgery, the First Afﬁliated Hospital of Naval Medical University, Shanghai 200433, China. E-mail: [runzhihuang2022@163.com](runzhihuang2022@163.com) G Xu and X Pan, Department of Urology, Xinhua Hospital Afﬁliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. E-mail: [xuguofeng@xinhuamed.com.cn](xuguofeng@xinhuamed.com.cn) and [panxiuwu@126.com](panxiuwu@126.com) aEqual contributors and co-First authors. Received 21 July 2024; Revised 29 August and 18 September 2024; Accepted 19 September 2024 doi: 10.1002/cti2.70009 Clinical & Translational Immunology 2024; 13: e70009 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 atthe 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. Keywords: biomarker, kidney neoplasm, LAG3, pan-cancer analysis, retrospective clinical study ª 2024 The Author(s) . Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of 2024 | Vol. 13 | e70009 Australian and New Zealand Society for Immunology, Inc. Page 1 INTRODUCTION Lymphocyte activation gene 3 (LAG3) is a type Itransmembrane protein located on activated NK and T-cell lines, mediating T-cell inhibition through its interaction with major histocom

FAQs

What is the main objective of this study regarding LAG3?

To clarify the role of LAG3 at a pan-cancer level by examining its prognostic significance and immunological associations across many cancer types.

How was LAG3 prognostic impact evaluated in the clinical cohort?

Through immunohistochemistry in a retrospective cohort of 370 patients, followed by Kaplan–Meier survival analysis and multivariate Cox regression.

What did pan-cancer analyses reveal about LAG3 and tumor biology?

LAG3 showed robust correlations with survival and tumor stages, strong links with immune-related genes and pathways, associations with immune cell infiltration patterns, and relationships with tumor mutation burden and microsatellite instability.

Sep 21, 2026

Uploaded by Riley