{"title":"Downregulation of autophagy is associated with poor clinical outcome after immunochemotherapy in patients with diffuse large B-cell lymphoma.","authors":"Ya-Li Zhang, Meng-Xue Ma, Li-Na Xing, Jing-Nan Zhang, Xiao-Nan Guo, Shukai Qiao","doi":"10.1016/j.exphem.2024.104638","DOIUrl":null,"url":null,"abstract":"<p><p>This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL (n=60) and patients with reactive lymphoproliferative disease (RLD; n=20) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in patients with RLD compared to those with DLBCL, but the difference was not statistically significant (P>0.05). p62 levels in patients with DLBCL were significantly higher than those in patients with RLD (P<0.05). Beclin-1 expression was associated only with the Ann Arbor stage (P<0.05), whereas p62 expression was associated with the Ann Arbor stage, International Prognostic Index score, extranodal involvement, and Ki-67 index (P<0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in patients with DLBCL. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (P>0.05). However, high p62 expression in patients with DLBCL was associated with reduced 2-year PFS compared with that of patients with low p62 expression (P<0.05); the 2-year OS was not affected (P>0.05). Our results demonstrate that autophagic activity affects the prognosis of patients with DLBCL; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of patients with DLBCL.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.exphem.2024.104638","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL (n=60) and patients with reactive lymphoproliferative disease (RLD; n=20) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in patients with RLD compared to those with DLBCL, but the difference was not statistically significant (P>0.05). p62 levels in patients with DLBCL were significantly higher than those in patients with RLD (P<0.05). Beclin-1 expression was associated only with the Ann Arbor stage (P<0.05), whereas p62 expression was associated with the Ann Arbor stage, International Prognostic Index score, extranodal involvement, and Ki-67 index (P<0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in patients with DLBCL. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (P>0.05). However, high p62 expression in patients with DLBCL was associated with reduced 2-year PFS compared with that of patients with low p62 expression (P<0.05); the 2-year OS was not affected (P>0.05). Our results demonstrate that autophagic activity affects the prognosis of patients with DLBCL; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of patients with DLBCL.
期刊介绍:
Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.