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

PURPOSE

CD58, a ligand of the CD2 receptor on T cells and NK 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.

MATERIALS AND METHODS

The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Ultimately, 3025 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 NGS and gene expression were analyzed via RNA-seq.

RESULTS

We found that 8.2% (250/3025) of patients were CD58mut in integrated cohort, whereas 11.3% (23/202) in JSPH cohort. CD58mut patients exhibit inferior progression-free survival (PFS) (the integrated cohort: HR=0.96,95% CI:0.77-1.20, p=0.663 the JSPH cohort: HR=1.85,95% CI:0.85-4.04, p=0.052) and overall survival (OS) (the integrated cohort: HR=1.43,95% CI:1.15-1.77, p<0.001; the JSPH cohort: HR=2.40,95% CI:0.83-6.93, 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.

CONCLUSION

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.