The prognostic significance of MYC/BCL2 double expression in DLBCL in the genetic classification era.

IF 5.7 2区 医学 Q1 Medicine
Cancer Science Pub Date : 2024-11-04 DOI:10.1111/cas.16377
Yi-Fan Wu, Qun-Hui Yuan, Hao-Rui Shen, Kai-Xin Du, Chun-Yu Shang, Yue Li, Xin-Yu Zhang, Jia-Zhu Wu, Rui Gao, Li Wang, Jian-Yong Li, Hua Yin, Jin-Hua Liang, Wei Xu
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Abstract

Double expression (DE) is a World Health Organization-recognized adverse prognostic factor in diffuse large B-cell lymphoma (DLBCL). However, the prognostic value of DE in the genetic subtyping era and potential mechanisms remain to be explored. We enrolled 246 DLBCL patients diagnosed between December 2021 and September 2023 in a Jiangsu Province Hospital cohort and included 930 DLBCL patients from three published studies in an external cohort. Double-expression DLBCL (DEL) in the external cohort was mainly distributed in the OTHER subtype (42.0%), EZB subtype (28.3%), and MCD subtype (15.0%), whereas the MCD subtype exhibited the highest ratio of DEL. DEL was significantly related to unfavorable overall survival (OS) and progression-free survival (PFS) in DLBCL, but only in EZB and OTHER subtypes that DEL retained remarkably adverse impacts on survivals compared to non-DEL. We explored the prognostic value of clinical and genetic parameters in DEL patients and found only ST2 showed better OS than A53 in DEL patients, whereas the other subtypes showed no significant difference. DEL showed similarities with the MCD subtype in mutation profiles. Furthermore, RNA-sequencing analyses exhibited upregulation in tumor proliferation-related pathways in DEL patients, but downregulation in extracellular matrix organization, T-cell activation and proliferation, type II interferon production, and pathways associated with cell death might contribute to the poor outcomes of DEL patients.

基因分类时代 DLBCL 中 MYC/BCL2 双重表达的预后意义。
双重表达(DE)是世界卫生组织公认的弥漫大B细胞淋巴瘤(DLBCL)的不良预后因素。然而,DE在基因亚型时代的预后价值和潜在机制仍有待探索。我们在江苏省医院的队列中纳入了2021年12月至2023年9月期间确诊的246例DLBCL患者,并在外部队列中纳入了来自三项已发表研究的930例DLBCL患者。外部队列中的双表达DLBCL(DEL)主要分布于OTHER亚型(42.0%)、EZB亚型(28.3%)和MCD亚型(15.0%),而MCD亚型的DEL比例最高。在DLBCL中,DEL与不利的总生存期(OS)和无进展生存期(PFS)明显相关,但只有在EZB和OTHER亚型中,与非DEL相比,DEL才对生存期有明显的不利影响。我们探讨了DEL患者临床和遗传参数的预后价值,发现在DEL患者中,只有ST2的OS优于A53,而其他亚型无明显差异。DEL与MCD亚型在突变特征上有相似之处。此外,RNA序列分析显示,DEL患者肿瘤增殖相关通路上调,但细胞外基质组织、T细胞活化和增殖、II型干扰素产生以及细胞死亡相关通路下调,这可能是导致DEL患者预后不佳的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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