Identification of FAT4 as a positive prognostic biomarker in DLBCL by comprehensive genomic analysis.

The molecular landscapes of diffuse large B-cell lymphoma (DLBCL) remained to be comprehensively investigated with an urgent need to identify novel prognostic biomarkers guiding prognostic stratification and disease monitoring. Baseline tumor samples of 148 DLBCL patients were analyzed using targeted next-generation sequencing (NGS) for mutational profiling, whose clinical reports were retrospectively reviewed. In this cohort, the subgroup of old DLBCL patients (age at diagnosis > 60, N = 80) exhibited significantly higher Eastern Cooperative Oncology Group scores and International Prognostic Index than their young counterparts (age at diagnosis ≤ 60, N = 68). As revealed by the NGS results, PIM1 (43.9%), KMT2D (31.8%), MYD88 (29.7%), and CD79B (27.0%) were identified as the most frequently mutated genes. Aberrations of genes of the immune escape pathway were significantly enriched in the young subgroup, while the altered epigenetic regulators were more abundant in the old patients. FAT4 mutation was identified as a positive prognostic biomarker, associated with longer progression-free survival and overall survival in the entire cohort and the old subgroup, using the Cox regression analyses. However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research.

Mutational Spectrum and Prognosis Analysis of Young Patients with Diffuse Large B-Cell Lymphoma Based on Next-Generation Sequencing / 中国实验血液学杂志

OBJECTIVE@#To investigate the mutational spectrum in young patients with diffuse large B-cell lymphoma (DLBCL) based on next generation sequencing (NGS), and to provide a basis for in-depth understanding of the molecular biological characteristics and accurate prognosis of young DLBCL.@*METHODS@#From March 2009 to March 2021, 68 young DLBCL patients with complete initial diagnosis data from the Department of Hematology, The People's Hospital Xinjiang Uygur Autonomous Region were retrospectively analyzed, and their paraffin-embedded tissues were subjected to targeted sequencing analysis by NGS technology (including 475 Target genes), and the differences in gene mutation profiles and signaling pathways between high-risk patients with aaIPI ≥2 and low-intermediate risk patients with aaIPI <2 were compared.@*RESULTS@#A total of 44 high-frequency mutation genes were detected in 68 young DLBCL patients. By comparing the high-frequency mutation genes in aaIPI high-risk group and low-intermediate risk group, it was found that CARD11 mutation in aaIPI high-risk group was significantly higher than that in low-intermediate risk group (P =0.002), while MGA mutation (P =0.037) only appeared in the aaIPI high-risk group, and SPEN mutation (P =0.004) only appeared in the aaIPI low-intermediate risk group. The high-frequency mutation genes and clinical indicators of the aaIPI high-risk group were included in the survival analysis, and the results showed that TP53 (P =0.009, P =0.027), POU2AF1 (P =0.003, P =0.006) and CCND3 (P =0.040, P =0.014) genes mutations were associated with worse PFS and OS, while B2M was associated with better PFS (P =0.014) and OS (P =0.013). Multivariate COX regression analysis showed that the TP53, POU2AF1 and CCND3 were independent risk factors for PFS（P ＝0.021，P =0.005，P =0.020） and OS（P ＝0.042，P =0.010，P =0.013）.@*CONCLUSION@#The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.

Distribution and prognostic value of LymphGen genotyping in patients with diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To investigate the distribution characteristics of LymphGen genotyping in a diffuse large B-cell lymphoma (DLBCL) population and verify its prognostic value. Methods: We collected the clinical data and paraffin-embedded tumor tissue samples of 155 patients with newly diagnosed DLBCL in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. DNA was extracted from tumor tissue and 475 gene mutations were detected by next-generation sequencing technology. We investigated the distribution of LymphGen genotyping in the DLBCL population, patients with different COO genotypes in the Xinjiang region, and their effects on PFS and OS. Results: ①Among 155 patients, 105 patients (67.7%) could be genotyped, including 14 (9.0%) for MCD, 26 (16.8%) for BN2, 10 (6.5%) for N1, 8 (5.2%) for EZB, 27 (17.4%) for A53, and 20 (12.9%) for ST2. ②The distribution of each gene subtype was different in different cell origin (COO) types (P=0.021) . ST2 was dominant in the germinal center type (GCB) group (28.8%) , and A53 and MCD were dominant in the non-GCB group (35.8%, 17.0%) . The BN2 type was the most common in both groups (23.1%, 26.4%) . ③There were statistically significant differences in progression-free survival (PFS) and overall survival (OS) among different gene subtypes (P=0.031 and 0.005, respectively) . N1 and A53 had poor prognosis. The 2-year PFS and OS rates of N1 were both (21.3±18.4) %, and the 3-year PFS and OS rates of A53 were (60.9±11.3) %, (46.8±10.9) %, respectively. ④ The 3-year PFS and OS rates of MCD were the best, but the 5-year PFS and OS rates were worse. ⑤In the ROC curve of LymphGen genotyping for OS prediction, the AUC was 0.66, showing a certain degree of differentiation. Conclusion: LymphGen genotyping in the DLBCL population was different from previous reports and was of great significance for the prognosis of patients with DLBCL.

Blood pressure variability in the acute ischemic stroke：predictive value and intervention target / 国际脑血管病杂志

Patients w ith acute ischemic stroke often have increased blood pressure and cause sharp fluctuations in blood pressure. Analysis of blood pressure variability can quantize the degree of blood pressure fluctuations w ithin a certain period of time and provide reliable predictive information for the outcomes of ischemic stroke. While reducing the average value of blood pressure, decreasing the blood pressure variability can make the patients obtain greater benefits. This article review s the possibility of blood pressure variability in patients w ith acute ischemic stroke for its predictive value and the blood pressure variability as an intervention target.