Gene Mutant Profile And Prognosis Analysis Of Elderly Patients With Diffuse Large B-cell Lymphoma Based On Second-generation Sequencing Technology

Objective:Second generation sequencing(NGS)was used to investigate gene mutation and prognostic significance in elderly patients with diffuse large B-cell lymphoma(DLBCL).Methods:Clinical data and paraffin-embedded tumor tissue samples were collected from 148 newly diagnosed and complete DLBCL patients in hematology Department of Xinjiang Uygur Autonomous Region People’s Hospital from March 2011 to March 2021.DNA was extracted from tumor tissue and targeted sequencing analysis(including 475 target genes)was performed using NGS technology.Differences in gene mutant profiles and signaling pathways were compared between older patients(>60 years)and younger patients(≤60 years),univariate Kaplan-Meier method and multivariate Cox regression were used to analyze the influencing factors of poor prognosis in the two groups.Results:(1)Compared with young DLBCL patients,the elderly patients showed higher IPI score,ECOG≥2 score,and a higher percentage of double-expression subtypes.(2)NGS results showed that a total of 40 high-frequency mutated genes were detected in148 DLBCL patients,among which PIM1(43.9%),KMT2D(31.8%),MYD88(29.7%),CD79B(27.0%)were the most frequently mutated genes.In this study,DLBCL patients could be genotyped according to quad type,including MCD subtype(45.3%),BN2subtype(25.7%),EZB subtype(15.5%),N1 subtype(6.1%),and 49 cases(33.1%)without classification.(3)By comparing the gene mutation profiles of elderly and young DLBCL patients,it was found that both of them had similarities but also heterogeneity.Both of them contained a large number of low-frequency mutant genes(<10%),and the distribution of gene mutation types was similar,and both were dominated by missense mutations.ATM(P=0.008)and DNMT3A(P=0.016)mutations were detected only in older patients,whereas B2M(P=0.020),CD70(P=0.035),NFKBIA(P=0.024),and STAT6(P=0.024)mutations were more common in younger patients.(4)According to the classification of signaling pathways,it was found that epigenetic regulation path-related mutations were more common in elderly patients than in young patients(P=0.02),and the immune escape pathway was significantly enriched in young patients(P=0.03).(5)Univariate survival analysis and multivariate Cox regression analysis for clinical features and high frequency mutated genes(>10%)in elderly and young DLBCL respectively showed that TP53 mutations were associated with shorter PFS in elderly DLBCL patients,while FAT4 mutations were associated with longer PFS in elderly DLBCL patients.(6)In elderly DLBCL patients,the combination analysis of FAT4 and TP53 mutations showed that FAT4 mutations had more prominent prognostic value of PFS.(7)In DLBCL,JAK-STAT pathway including FAT4 gene has good prognostic value.Conclusions: This study provides an understanding of the gene mutant profiles of elderly and young DLBCL patients,and reveals the differences in gene mutant profiles and signaling pathways between elderly and young DLBCL patients,providing a basis for further understanding of the molecular biological characteristics,accurate prognosis and treatment of elderly DLBCL patients.Conclusion:There are differences in clinical features,gene mutant spectrum and signaling pathways between elderly and young patients with diffuse large B-cell lymphoma.A new favorable prognostic biomarker FAT4 has been found for the first time in elderly DLBCL patients.FAT4 mutation is more prominent in predicting the prognosis of PFS in elderly patients with negative TP53,which provides a basis for accurate prognostic judgment in elderly DLBCL patients.