Lymphocyte activating gene ۳ (LAG-۳) asa potential marker of prognosis and tumor progression insolid tumors: A meta-analysis

Background: Lymphocyte activating gene ۳ (LAG-۳) is animmune checkpoint protein and a potential target for immunecheckpoint inhibition, with an underlying role in tumor progressionand cancer prognosis. The expression of LAG-۳ in solidtumors has been investigated in many cancer types; however,the results have been heterogeneous. The objective of this metaanalysisis to evaluate the pooled association between LAG-۳expression levels and prognosis and tumor progression in solidtumors.Materials and Methods: A systematic literature search wasconducted using PubMed, Scopus, and Web of Science databasesfrom inception to December ۲۰۲۲. Studies that reported theassociation of LAG-۳ expression levels with overall survival(OS) or disease-free survival (DFS) in patients with solid tumorswere included. Random effect meta-analysis was used tocompute the pooled hazard ratios (HRs) of LAG-۳ expressionas a predictor of clinical outcome. Subgroup analyses based onthe tumor type and site and sensitivity analysis were performed.Results: A total of ۳۸ studies, including ۱۱۰۹۳ patients, wereincluded in the meta-analysis. Pooled analysis suggested thathigh LAG-۳ expression was significantly associated with poorOS (HR= ۱.۱۱, ۹۵% CI: ۱.۰۱-۱.۲۲, P-value= ۰.۰۳) in patientswith solid tumors. However, no significant association betweenLAG-۳ and DFS was obtained. In addition, the overall pooledanalysis indicated that high LAG-۳ expression was significantlyassociated with the TNM stage (OR: ۱.۳۹, CI: ۱.۰۸-۱.۸۰, P-value=۰.۰۱) and tumor differentiation (OR: ۱.۵۴, CI: ۱.۰۴-۲.۲۹, Pvalue:۰.۰۳). Stratified analysis based on tumor types suggestedthat high LAG-۳ expression was significantly associated withpoor OS in hepatocellular carcinoma, renal cell carcinoma, andbladder cancer, whereas it was significantly associated with a better DFS in colorectal cancer.Conclusion: The present study indicates that while LAG-۳ expressionhas a generally weak but significant association withtumor progression and worse survival, its prognostic effect indifferent types of solid tumors is heterogeneous.

کلیدواژه ها:

Lymphocyte activating gene ۳ (LAG-۳) ، survival ، tumor progression ، solid tumor ، immune checkpoint inhibitor