CD137 Protein Expression Pattern Determines the Functional Role of Galectin-9 in Colorectal Cancer.

IF 3 2区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yongping Huang, Xue Huang, Zhengming Zhu, Wubulikasimu Wulamu, Kai Huang, Dejun Tang, Jinlong Yu
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引用次数: 0

Abstract

The rapid advancement of single-cell sequencing technology has generated extensive data, providing critical resources for colorectal cancer (CRC) research. This study conducts a detailed analysis of CRC single-cell sequencing data to develop a novel clinical prognostic tool and explore potential therapeutic targets for the LGALS9 gene. Using the Scissor algorithm, we created a CRC prognostic scoring system (SDRS) based on 13 key genes, with particular focus on LGALS9 and its protein, Galectin-9, in mice CRC model with altered CD137 expression. Our findings demonstrate that the SDRS accurately reflects clinical and pathological features of CRC patients, acting as an independent predictor of outcomes. LGALS9 expression is generally reduced in CRC tissues and is associated with poorer prognosis. We also observed a strong positive correlation between LGALS9 and CD137 expression, with CD137 showing significant variability in CRC tissues. In mouse models with CD137 overexpression, Galectin-9 treatment led to notable antitumor effects and increased infiltration of activated T cells. In contrast, in CD137-deficient models, Galectin-9 promoted tumor growth with limited T cell presence. These results suggest that the role of LGALS9 in CRC may depend on CD137 expression, highlighting the potential of LGALS9 as a therapeutic target. CD137 levels may serve as a key indicator for predicting the effectiveness of this treatment strategy.

CD137蛋白表达模式决定了Galectin-9在结直肠癌中的功能作用
单细胞测序技术的快速发展产生了大量数据,为结直肠癌(CRC)研究提供了重要资源。本研究对 CRC 单细胞测序数据进行了详细分析,以开发一种新型临床预后工具,并探索 LGALS9 基因的潜在治疗靶点。利用剪刀算法,我们创建了基于13个关键基因的CRC预后评分系统(SDRS),尤其关注CD137表达改变的小鼠CRC模型中的LGALS9及其蛋白Galectin-9。我们的研究结果表明,SDRS 准确反映了 CRC 患者的临床和病理特征,是预测预后的独立指标。LGALS9 在 CRC 组织中的表达普遍降低,与较差的预后相关。我们还观察到 LGALS9 和 CD137 的表达之间存在很强的正相关性,CD137 在 CRC 组织中的表达也存在显著差异。在 CD137 过表达的小鼠模型中,Galectin-9 治疗可产生显著的抗肿瘤效果,并增加活化 T 细胞的浸润。相反,在 CD137 缺失的模型中,Galectin-9 促进了肿瘤的生长,但 T 细胞的存在却很有限。这些结果表明,LGALS9在CRC中的作用可能取决于CD137的表达,突出了LGALS9作为治疗靶点的潜力。CD137水平可作为预测这种治疗策略有效性的关键指标。
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来源期刊
Molecular Carcinogenesis
Molecular Carcinogenesis 医学-生化与分子生物学
CiteScore
7.30
自引率
2.20%
发文量
112
审稿时长
2 months
期刊介绍: Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
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