Identification and Validation of a DNA Damage Repair-Related Signature for Diffuse Large B-Cell Lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma in adults, whose prognostic scoring system remains to be improved. Dysfunction of DNA repair genes is closely associated with the development and prognosis of diffuse large B-cell lymphoma. The aim of this study was to establish and validate a DNA repair-related gene signature associated with the prognosis of DLBCL and to investigate the clinical predictive value of this signature. Methods: DLBCL cases were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. One hundred ninety-nine DNA repair-related gene sets were retrieved from the GeneCards database. The LASSO Cox regression was used to generate the DNA repair-related gene signature. Subsequently, the level of immune cell infiltration and the correlation between the gene signature and immune cells were analyzed using the CIBERSORT algorithm. Based on the Genomics of Drug Sensitivity in Cancer (GDSC) database, the relationship between the signature and drug sensitivity was analyzed, and together with the nomogram and gene set variation analysis (GSVA), the value of the signature for clinical application was evaluated. Results: A total of 14 DNA repair genes were screened out and included in the final risk model. Subgroup analysis of the training and validation cohorts showed that the risk model accurately predicted overall survival of DLBCL patients, with patients in the high-risk group having a worse prognosis than patients in the low-risk group. Subsequently, the risk score was confirmed as an independent prognostic factor by multivariate analysis. Furthermore, by CIBERSORT analysis, we discovered that immune cells, such as regulatory T cells (Tregs), activated memory CD4+ T cells, and gamma delta T cells showed significant differences between the high- and low-risk groups. In addition, we found some interesting associations of our signature with immune checkpoint genes (CD96, TGFBR1, and TIGIT). By analyzing drug sensitivity data in the GDSC database, we were able to identify potential therapeutics for DLBCL patients stratified according to our signature. Conclusions: Our study identified and validated a 14-DNA repair-related gene signature for stratification and prognostic prediction of DLBCL patients, which might guide clinical personalization of treatment.

DDGP followed by radiotherapy vs VIPD followed by radiotherapy in newly diagnosed early NK/T-cell lymphoma.

PURPOSE: To explore the best treatment for early natural killer/T (NK/T)-cell lymphoma, we compared the efficacy and safety of DDGP (pegaspargase, gemcitabine, cisplatin and dexamethasone) followed by radiotherapy (RT) and VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone) followed by radiotherapy for newly diagnosed patients. MATERIALS AND METHODS: 40 newly diagnosed patients with stage I-II from January 2011 to November 2016 were treated with DDGP followed by radiotherapy or VIPD followed by radiotherapy. They were assessed in this study. RESULTS: The complete response rate (CRR) and overall response rate (ORR) of the DDGP followed by radiotherapy group were higher than those of the VIPD followed by radiotherapy group (CRR: 85 % vs 50 %, P = 0.018; ORR: 95 % vs 65 %, P = 0.048). The 5-year progression-free survival (PFS) rate was better in the DDGP followed by radiotherapy group (83.3 % vs 44.4 %, χ2 = 7.809, P = 0.005). There was no significant difference in the 5-year overall survival (OS) rate between the two groups (83.0 % vs 72.1 %, χ2 = 0.231, P = 0.631). Treatment method (P = 0.011) and IPI score (P = 0.027) were independent risk factors for PFS. The DDGP followed by radiotherapy group was more prone to grade I-II clotting dysfunction (P = 0.004). CONCLUSIONS: In patients newly diagnosed with early NK/T-cell lymphoma, those treated with DDGP followed by radiotherapy had a higher CRR and ORR and longer PFS than those treated with VIPD followed by radiotherapy, and adverse reactions were tolerable.

[The Effect of Bcl-6 Expression on the Prognosis of Newly Treated Double-Expressing Lymphoma Treated with R-CHOP Regimen].

OBJECTIVE: To compare the treatment outcome and prognosis of the newly-treated myc+/bcl-2+/bcl-6- lymphoma (bcl-6- double-expression lymphoma, bcl-6- DEL) and myc+/bcl-2+/bcl-6+ co-expression lymphoma (bcl-6+ double-expression lymphoma, bcl-6+ DEL) patients treated by R-CHOP. METHODS: 152 double-expression lymphoma patients (myc+/bcl-2+) treated in the Oncology Department of the First Affiliated Hospital of Zhengzhou University from September 2016 to June 2020 were selected. The short-term efficacy and long-term survival between the patients with bcl-6- DEL and bcl-6+ DEL was analyzed. RESULTS: The median age of 152 DEL patients was 60.5 years old (15-87 years old). 85 patients (55.9%) were Ann Arbor stage III/IV. There was no significant difference in clinical data between the patients in the two groups. Multivariate Cox regression analysis showed that bcl-6 expression, ECOG score, and stage were the independent prognostic factors for the entire group of DEL patients. There was no statistical difference in ORR between the patients in the two groups (χ2=0.749, P=0.387). Kaplan-Meier survival analysis showed that PFS and OS of the bcl-6+ DEL group were significantly higher than those in bcl-6- DEL group (PFS: χ2=6.095, P=0.014; OS: χ2=5.133, P=0.023). CONCLUSION: bcl-6+ is a good prognostic factor for DEL. The long-term curative effect of newly-treated bcl-6+ DEL patients treated by R-CHOP regimen is higher than those with bcl-6- DEL patients.