Novel Prognostic Biomarkers CD24 And LncRNA XIST For Activated B-cell Like Diffuse Large B-cell Lymphoma

Background:Diffuse large B-cell lymphoma(DLBCL)is the most common nonHodgkin’s lymphoma and of which the prognosis of activated B-cell-like(ABC)subtype is poor.Although R-CHOP significantly improves the survival of patients with DLBCL,20%to 40%of patients were resistant to R-CHOP therapy.Thus,screening for candidate therapeutic targets for R-CHOP resistant patients is urgent.The previous researches have shown that CD24 is related to the development,invasion,and metastasis of cancer.Our project aims to clarify the relationship between CD24 and ABC-DLBCL.Material and methods:The expression of CD24 mRNA in 118 ABC-DLBCL cases treated with R-CHOP was detected by RNAscope,and the relationship between CD24 expression and R-CHOP treatment response was analyzed.The correlation between CD24 expression and treatment efficiency was further analyzed by data downloaded from the Gene Expression Omnibus(GEO)database.The association between CD24 expression and immune response was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts(CIBERSORT)methodology and Gene Ontology(GO)biological process(BP)analysis.Results:The positive expression rate of CD24 mRNA in ABC-DLBCL patients was 38.1%(45/118).Complete Response(CR)rate was significantly higher in patients with CD24 high expression than those with CD24 low expression(P=0.039;44.4%vs 26.0%).CR rate was significantly different between CD24 high and low expression groups in the analysis of GEO datasets(P=0.003;83.2%vs 58.0%).The CD24 high expression patients had significantly lower proportions of T cells and nonspecific immune cells in the CIBERSORT analysis.In addition,T-helper 2 cell differentiation and monocyte chemotaxis were repressed in CD24 high expression group in the GO-BP analysis.Conclusions:CD24 was correlated with better R-CHOP treatment response and tumor immunosuppression in ABC-DLBCL.CD24 may be a promising signal in treatment and prognosis evaluation in ABC-DLBCL patients.Background:One-third of activated B-cell like diffuse large B-cell lymphoma(ABC-DLBCL)patients do not respond well to standard first-line therapy.Hence,identifying biomarkers to evaluate therapeutic efficacy and warn of the emergence of drug resistance is crucial.Through early-stage screening,long non-coding RNA(lncRNA)X-inactive specific transcript(XIST)was found to be correlated with treatment response.This study aimed to clarify the characteristics of XIST in ABC-DLBCL patients.Methods:The expression level of XIST in 161 ABC-DLBCL patients who received R-CHOP therapy was examined by RNA in situ hybridization,and the connections between XIST expression and pathophysiological features,treatment response and prognosis were analyzed in our cohort and the GEO cohort.Cell biology experiments and bioinformatics analyses were conducted to determine aberrant signaling.Results:The proportion of complete response(CR)in patients with high XIST expression was significantly lower than that in patients with low XIST expression(53.8%vs.77.1%)(P=0.002).The high expression of XIST was remarkably associated with the characteristics of tumor progression and was an independent prognostic element for OS(P=0.039)and PFS(P=0.027)in ABC-DLBCL.Knockdown of XIST repressed ABCDLBCL cellular proliferation through regulating Raf/MEK/ERK signaling.XIST was also proven to be involve in m6A-related methylation and ATF6-associated autophagy.Conclusions:High expression of XIST was associated with ABC-DLBCL tumorigenesis and development,and contributed to R-CHOP treatment resistance.XIST may be a promising signal to predict ABC-DLBCL prognosis and a potential target for ABC-DLBCL therapy.