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司他汀的上调与预后不良相关,并促进眼眶弥漫性大B细胞淋巴瘤的肿瘤进展。

Upregulation of stomatin is associated with poor prognosis and promotes tumor progression of orbital diffuse large B-cell lymphoma.

作者信息

Chen Wen, Chi Jingyi, Song Weichen, Li Xiuyun, Ma Jinlei, Liu Xinyu, Xiao Lihua, Zhu Wenwen

机构信息

Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China.

Clinical Research Center, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China.

出版信息

Front Oncol. 2025 May 23;15:1596614. doi: 10.3389/fonc.2025.1596614. eCollection 2025.

DOI:10.3389/fonc.2025.1596614
PMID:40485728
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12141002/
Abstract

INTRODUCTION

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin's lymphoma that predominantly affects the elderly and carries a poor prognosis. When arising in the orbit, DLBCL is characterized by rapid growth, high invasiveness, and a risk of severe vision loss. Despite the use of the R-CHOP regimen, long-term survival outcomes remain suboptimal, highlighting the need for new prognostic biomarkers and therapeutic targets.

METHODS

We explored stomatin as a potential prognostic biomarker and therapeutic target for orbital DLBCL. Stomatin expression was analyzed using the GEO database (GSE83632), and Mendelian randomization (MR) analysis was conducted to assess its causal relationship with DLBCL. Immunohistochemistry (IHC) was performed on orbital DLBCL specimens to evaluate stomatin expression. The functional role of stomatin was examined through siRNA-mediated knockdown in DLBCL cell lines, followed by validation using quantitative RT-PCR and Western blot. Cell proliferation, invasion, migration, and apoptosis were assessed using CCK-8, Transwell assays, and flow cytometry.

RESULTS

Database analysis revealed elevated stomatin expression in DLBCL, and MR analysis suggested a positive causal association with disease development. IHC confirmed significantly increased stomatin expression in orbital DLBCL tissues, which was associated with poor prognosis based on survival analysis. Vitro assays demonstrated that stomatin knockdown significantly inhibited cell proliferation, migration, and invasion while promoting apoptosis.

DISCUSSION

Our findings indicate that stomatin contributes to orbital DLBCL progression and is associated with adverse clinical outcomes. Stomatin may serve as both a prognostic biomarker and a potential therapeutic target for this malignancy.

摘要

引言

弥漫性大B细胞淋巴瘤(DLBCL)是非霍奇金淋巴瘤的一种侵袭性亚型,主要影响老年人,预后较差。当发生于眼眶时,DLBCL的特点是生长迅速、侵袭性强且有严重视力丧失的风险。尽管使用了R-CHOP方案,但长期生存结果仍不理想,这凸显了对新的预后生物标志物和治疗靶点的需求。

方法

我们探索了stomatin作为眼眶DLBCL潜在的预后生物标志物和治疗靶点。使用GEO数据库(GSE83632)分析stomatin表达,并进行孟德尔随机化(MR)分析以评估其与DLBCL的因果关系。对眼眶DLBCL标本进行免疫组织化学(IHC)检测以评估stomatin表达。通过在DLBCL细胞系中进行siRNA介导的敲低来研究stomatin的功能作用,随后使用定量RT-PCR和蛋白质免疫印迹法进行验证。使用CCK-8、Transwell实验和流式细胞术评估细胞增殖、侵袭、迁移和凋亡。

结果

数据库分析显示DLBCL中stomatin表达升高,MR分析表明其与疾病发展呈正因果关联。IHC证实眼眶DLBCL组织中stomatin表达显著增加,基于生存分析,这与预后不良相关。体外实验表明,stomatin敲低显著抑制细胞增殖、迁移和侵袭,同时促进凋亡。

讨论

我们的研究结果表明,stomatin促进眼眶DLBCL进展,并与不良临床结果相关。stomatin可能既是这种恶性肿瘤的预后生物标志物,也是潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/de9e1000b368/fonc-15-1596614-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/9f17fd61228c/fonc-15-1596614-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/f9c047c0ba72/fonc-15-1596614-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/de9e1000b368/fonc-15-1596614-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/9f17fd61228c/fonc-15-1596614-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/1b362e32c5cf/fonc-15-1596614-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/1c4b0280a468/fonc-15-1596614-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/fb2d7b89b63a/fonc-15-1596614-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/f9c047c0ba72/fonc-15-1596614-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f8/12141002/de9e1000b368/fonc-15-1596614-g007.jpg

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