Effect of PLA1A as a core gene synergizing TIGIT with PD-1 in improving immunotherapy response and prognosis in colorectal cancer

WU Han; FAN Peiwen; FENG Yaning; WANG Ruozheng

doi:10.3969/j.issn.1674-4136.2025.02.014

Abstract：Objective To identify key molecules associated with the immune microenvironment by analyzing the expression correlation between PD-1 and immune checkpoints(e.g.:2B4,KLRG1)in CD4+/CD8+T cells,explore their mechanisms in colorectal cancer(CRC)immunotherapy,and identify core genes to provide potential therapeutic targets.Methods Flow cytometry was used to detect the expression levels of PD-1,TIGIT,and three other immune checkpoints in CD4+/CD8+T cells from tumor tissues and peripheral blood of 29 CRC patients.The TCGA colorectal cancer dataset(COAD/READ)was integrated for differential gene validation,and LASSO-Cox regression model was applied to screen critical genes.The IMvigor210 immunotherapy cohort and additional cohorts were utilized to evaluate the correlation between gene expression,therapeutic response,and prognosis,with survival analysis performed via the Kaplan-Meier method.Results The high expression of PD-1 and TIGIT was positively correlated with CD4+/CD8+T cells(r=0.610,P＜0.001).In the IMvigor210 cohort,the high-expression group demonstrated a higher proportion of CR and PR(P=0.003),with elevated TIGIT/PD-1 co-expression levels in CR and PR subgroups(P＜0.01).LASSO and Cox regression analysis were used to identify ICOS,PLA1A,and GPX3 as core genes.High expression of PLA1A was associated with poor prognosis in CRC patients(HR=1.8,P＜0.05)but correlated with favorable outcomes in immunotherapy cohorts(HR=0.48,P＜0.05).Conclusions TIGIT/PD-1 co-expression may serve as a predictive biomarker for immunotherapy response.PLA1A likely exerts dual prognostic roles through microenvironment regulation,offering new basis for selecting immunotherapy targets in colorectal cancer.