基于mri的机器学习揭示蛋白酶体亚基psmb8通过激活TGFBR1/2-SMAD2/3轴介导的恶性胶质瘤表型。

IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Dongling Pei, Zeyu Ma, Yuning Qiu, Minkai Wang, Zilong Wang, Xianzhi Liu, Long Zhang, Zhenyu Zhang, Ran Li, Dongming Yan
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引用次数: 0

摘要

胶质瘤是中枢神经系统最常见和最具侵袭性的肿瘤,是有效治疗和患者预后的主要挑战。本研究确定了蛋白酶体亚基β -8型(PSMB8/LMP7)作为胶质瘤预后的一个有希望的生物标志物。利用术前磁共振成像(MRI)衍生的多参数放射学模型,我们准确预测了PSMB8的表达水平。值得注意的是,放射组学预测预后不良与PSMB8表达升高高度一致。我们的研究结果表明,PSMB8缺失不仅可以抑制胶质瘤细胞的增殖和迁移,还可以通过激活转化生长因子β (TGF-β)信号通路诱导细胞凋亡。这得到了关键受体(TGFBR1和TGFBR2)下调的支持。此外,干扰PSMB8的表达会损害SMAD2/3的磷酸化和核易位,SMAD2/3是TGF-β信号传导的关键介质。因此,这些分子改变导致肿瘤进展减少,对替莫唑胺(TMZ)(一种标准化疗药物)的敏感性增强。总之,我们的研究结果强调了PSMB8在胶质瘤病理生理中的关键作用及其作为预后标志物的潜力。本研究也证明了MRI放射组学在术前风险分层和预诊断中的临床应用。靶向抑制PSMB8可能是克服TMZ耐药性和改善胶质瘤患者预后的一种治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MRI-based machine learning reveals proteasome subunit PSMB8-mediated malignant glioma phenotypes through activating TGFBR1/2-SMAD2/3 axis.

Gliomas are the most prevalent and aggressive neoplasms of the central nervous system, representing a major challenge for effective treatment and patient prognosis. This study identifies the proteasome subunit beta type-8 (PSMB8/LMP7) as a promising prognostic biomarker for glioma. Using a multiparametric radiomic model derived from preoperative magnetic resonance imaging (MRI), we accurately predicted PSMB8 expression levels. Notably, radiomic prediction of poor prognosis was highly consistent with elevated PSMB8 expression. Our findings demonstrate that PSMB8 depletion not only suppressed glioma cell proliferation and migration but also induced apoptosis via activation of the transforming growth factor beta (TGF-β) signaling pathway. This was supported by downregulation of key receptors (TGFBR1 and TGFBR2). Furthermore, interference with PSMB8 expression impaired phosphorylation and nuclear translocation of SMAD2/3, critical mediators of TGF-β signaling. Consequently, these molecular alterations resulted in reduced tumor progression and enhanced sensitivity to temozolomide (TMZ), a standard chemotherapeutic agent. Overall, our findings highlight PSMB8's pivotal role in glioma pathophysiology and its potential as a prognostic marker. This study also demonstrates the clinical utility of MRI radiomics for preoperative risk stratification and pre-diagnosis. Targeted inhibition of PSMB8 may represent a therapeutic strategy to overcome TMZ resistance and improve glioma patient outcomes.

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CiteScore
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