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OBJECTIVE: To investigate the pathogenic role and underlying mechanisms of lncRNAs in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). METHODSï¼: RNA-sequencing (RNA-seq) was applied to screen the expression profile of lncRNAs in peripheral leukocytes from 5 AAV patients and 5 healthy controls (HC). Candidate lncRNAs were preliminarily verified in peripheral leukocytes from 46 AAV patients and 35 HC by qRT-PCR. Then, the identified LINC02193 was further validated in peripheral neutrophils from 67 AAV patients, 45 HC and 64 disease controls. Correlation between LINC02193 levels and disease activity was analyzed. Then, a loss-of-function study was conducted to investigate the role of LINC02193 in neutrophils activation. Furthermore, bioinformatics analysis, dual luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to explore the mechanism of LINC02193 regulating neutrophils activation. RESULTS: A total of 467 upregulated and 412 downregulated lncRNAs were identified in AAV patients. From top 5 upregulated lncRNAs, an elevation of LINC02193 was validated in a larger sample of AAV patients, and positively correlated with disease activity. Knockdown of LINC02193 inhibited ROS and NO production, NETs release and adhesion to endothelial cells of differentiated human promyelocytic leukaemia HL60 cells (dHL-60), whereas overexpression of ICAM1 counteracted these effects. Mechanistic analysis demonstrated that LINC02193 acted as a miR-485-5p sponge to relieve the repressive effect of miR-485-5p on ICAM1, thus promoting ICAM1 expression. CONCLUSION: LINC02193, a novel lncRNA identified in AAV could function as competing endogenous RNAs (ceRNA) for miR-485-5p to promote ICAM1 expression and neutrophils activation, suggesting its potential as a therapeutic target of AAV.
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The prognostic value of albumin changes between diagnosis and end-of-treatment (EoT) in diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 574 de novo DLBCL patients treated with R-CHOP from our and two other centers. All patients were divided into a training cohort (n = 278) and validation cohort (n = 296) depending on the source of the patients. Overall survival (OS) and progression-free survival (PFS) were analyzed by the method of Kaplan-Meier and Cox proportional hazard regression model. In the training cohort, 163 (58.6%) patients had low serum albumin at diagnosis, and 80 of them were present with consecutive hypoalbuminemia at EoT. Patients with consecutive hypoalbuminemia showed inferior OS and PFS (p = 0.010 and p = 0.079, respectively). Similar survival differences were also observed in the independent validation cohort (p = 0.006 and p = 0.030, respectively). Multivariable analysis revealed that consecutive hypoalbuminemia was an independent prognostic factor OS [relative risk (RR), 2.249; 95% confidence interval (CI), 1.441-3.509, p < 0.001] and PFS (RR, 2.001; 95% CI, 1.443-2.773, p < 0.001) in all DLBCL patients independent of IPI. In conclusion, consecutive hypoalbuminemia is a simple and effective adverse prognostic factor in patients with DLBCL, which reminds us to pay more attention to patients with low serum albumin at EoT during follow-up.
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Previous studies showed albumin at diagnosis could be used to predict outcome in patients with diffuse large B-cell lymphoma (DLBCL), but whether albumin could improve the international prognostic index (IPI) risk stratification remains unknown. Herein, we retrospectively analyzed 440 de novo DLBCL patients in this study. The cutoff value of albumin was 39.2 g/L. Patients with high serum albumin showed superior OS and PFS (p = 0.002 and p < 0.001, respectively). According to IPI, there were 163 patients (37.0%) in low-risk group, 107 (24.3%) in low-intermediate risk group, 114 (25.9%) in high-intermediate risk group and 56 (12.7%) in high-risk group. Further analysis showed high albumin could identify a subgroup of patients with extremely superior OS and PFS in low IPI risk patients (p = 0.022 and p = 0.034, respectively). Multivariate analysis revealed that high albumin was an independent prognostic factor for OS (relative ratio [RR] 0.122; 95% confidence interval [CI] 0.021-0.715, p = 0.020) and trend for PFS (RR 0.417; 95% CI 0.168-1.035, p = 0.059). In conclusion, our study suggests that albumin at diagnosis is a simple and effective prognostic factor in DLBCL patients, allowing the identification of a superior outcome subgroup in low-risk patients, which may help to guide treatment in clinical trial.