A Novel CD58 Mutation-Related Signature Predicts Prognosis Risk in Diffuse Large B-Cell Lymphoma Patients

CD58, a ligand of the CD2 receptor on T cells and natural killer cells, is abnormally expressed in diffuse large B-cell lymphoma (DLBCL). However, data on the value of CD58 mutation (CD58mut) in DLBCL are limited. Here, we aimed to evaluate the characteristics and prognostic value of CD58mut in DLBCL patients.

The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Ultimately, 3,025 DLBCL patients in published cohorts were enrolled in the final analysis. Among the 202 DLBCL patients in the Jiangsu Province Hospital (JSPH) cohort, all tumor tissue samples were collected to perform next-generation sequencing and gene expression was analyzed via RNA-seq.

We found that 8.2% (250/3,025) of patients were CD58mut in integrated cohort, whereas 11.4% (23/202) in the JSPH cohort. CD58mut patients exhibit inferior progression-free survival (the integrated cohort: hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.77 to 1.20; p=0.663 the JSPH cohort: HR, 1.85; 95% CI, 0.85 to 4.04; p=0.052) and overall survival (the integrated cohort: HR, 1.43; 95% CI, 1.15 to 1.77; p < 0.001; the JSPH cohort: HR, 2.40; 95% CI, 0.83 to 6.93; p=0.026). A model based on six signature genes (MRO, OXTR, RASL11A, RLN1, SIGLEC1, and PROM2) was constructed via machine learning. To optimize risk stratification and survival prediction for CD58mut patients, biological mechanism of the poorer prognosis in high-risk group may be related to the greater abundance of immunosuppressive cells, especially M2 macrophages.

Our results indicated that CD58mut could serve as a novel prognostic factor for DLBCL patients, and further exploration of personalized treatment strategies for high-risk DLBCL patients based on the risk score model is needed.