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识别用于预测结直肠癌预后、肿瘤浸润免疫细胞和化疗反应的乳酸化相关模型

英文原题:Identification of a lactylation-related model for predicting prognosis, tumor-infiltrating immune cells, and chemotherapy response in colorectal cancer.

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Identification of a lactylation-related model for predicting prognosis, tumor-infiltrating immune cells, and chemotherapy response in colorectal cancer.

PubMed 2026/01/07(内容时间) Naunyn Schmiedebergs Arch Pharmacol Q2 · IF 4(JCR 2025)

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中文摘要

结直肠癌(CRC)是癌症相关死亡的主要原因之一,其分子异质性持续阻碍着准确的预后评估和有效的治疗分层。新出现的证据表明,蛋白质乳酰化——一种近期发现的与代谢重编程相关的翻译后修饰——在多种癌症的肿瘤进展、免疫调节和治疗反应中发挥重要作用。

然而,其在 CRC 中的功能相关性和预后意义仍未得到充分表征。在本研究中,我们将乳酰化相关基因表达谱与单细胞 RNA 测序相结合,以识别能够优化 CRC 分子分型的新型生物标志物。差异表达分析揭示了 89 个乳酰化相关基因,其中五个关键基因——CALD1、S100A11、S100A6、LGALS1 和 CSRP2——与不良生存显著相关,并富集于糖酵解和碳代谢等通路中。基于这些基因的无监督聚类识别出两个稳健的 CRC 亚组,具有不同的免疫浸润模式和预后结局,并通过预后风险模型进一步验证。

我们的发现凸显了乳酰化相关生物标志物在增强 CRC 预后预测和治疗分层方面的潜力,为免疫调节和化疗耐药提供了新见解。本研究强调了将乳酰化特征纳入 CRC 分子谱分析以改善个体化治疗策略的重要性。

展开英文摘要原文

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, and its molecular heterogeneity continues to impede accurate prognostic assessment and effective treatment stratification. Emerging evidence indicates that protein lactylation, a recently identified post-translational modification linked to metabolic reprogramming, plays an important role in tumor progression, immune regulation, and therapeutic response in multiple cancers.

However, its functional relevance and prognostic significance in CRC remain insufficiently characterized. In this study, we integrated lactylation-related gene expression profiles with single-cell RNA sequencing to identify novel biomarkers capable of refining CRC molecular subtyping.

Differential expression analysis revealed 89 lactylation-associated genes, among which five key genes-CALD1, S100A11, S100A6, LGALS1, and CSRP2-were significantly associated with poor survival and enriched in pathways including glycolysis and carbon metabolism. Unsupervised clustering based on these genes identified two robust CRC subgroups with distinct immune infiltration patterns and prognostic outcomes, further validated by a prognostic risk model.

Our findings highlight the potential of lactylation-related biomarkers to enhance CRC prognostic prediction and therapeutic stratification, providing new insights into immune modulation and chemoresistance.

This study underscores the importance of incorporating lactylation features into CRC molecular profiling to improve personalized treatment strategies.

论文信息

作者
Zhu L、Jin S、Xia L、Bo W、Chi X
第一作者单位
The Affiliated Hospital of Changchun University of Chinese Medicine, No. 1478 Gongnong Road, Chaoyang District, Changchun City, Jilin Province, China.China
通讯作者单位
The Affiliated Hospital of Changchun University of Chinese Medicine, No. 1478 Gongnong Road, Chaoyang District, Changchun City, Jilin Province, China. 15948072446@163.com.China
期刊
Naunyn-Schmiedeberg's archives of pharmacology2026 Mar
原文标识
PubMed 41498838 · DOI 10.1007/s00210-025-04910-5