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

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.