Huang Yongping, Huang Xue, Zhu Zhengming, Wulamu Wubulikasimu, Huang Kai, Tang Dejun, Yu Jinlong
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Shenzhen & Longgang District People's Hospital of Shenzhen, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.
Mol Carcinog. 2025 Feb;64(2):226-243. doi: 10.1002/mc.23838. Epub 2024 Nov 6.
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.
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）研究提供了关键资源。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。使用剪刀算法，我们基于13个关键基因创建了一个CRC预后评分系统（SDRS），特别关注LGALS9及其蛋白半乳糖凝集素-9，在CD137表达改变的小鼠CRC模型中进行研究。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，是预后的独立预测指标。LGALS9在CRC组织中的表达通常降低，且与较差的预后相关。我们还观察到LGALS9与CD137表达之间存在强正相关，CD137在CRC组织中表现出显著变异性。在CD137过表达的小鼠模型中，半乳糖凝集素-9治疗导致显著的抗肿瘤作用，并增加了活化T细胞的浸润。相反，在CD137缺陷模型中，半乳糖凝集素-9在T细胞存在有限的情况下促进肿瘤生长。这些结果表明，LGALS9在CRC中的作用可能取决于CD137表达，突出了LGALS9作为治疗靶点的潜力。CD137水平可能是预测该治疗策略有效性的关键指标。
