Chang Huan, Zheng Ning, Zhu Xiaocheng
Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha 410000, Hunan, China.
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410000, Hunan, China.
Gene. 2025 Mar 5;939:149191. doi: 10.1016/j.gene.2024.149191. Epub 2024 Dec 25.
This study aimed to identify a lactylation-related gene signature for predicting prognosis and guiding therapies in colon adenocarcinoma (COAD). We seek to address the challenges in COAD prognostication due to tumor heterogeneity and variable treatment responses.
The study employed integrative bioinformatics analyses on multi-omics data from public databases, including gene expression profiles, clinical data, and lactylation-related genes (LRGs). The least absolute shrinkage and selection operator (LASSO) regression analysis and Cox risk model were applied to develop a prognostic signature. The predictive capabilities of the signature were assessed in four independent COAD cohorts (GSE39582, GSE71187, GSE75500, and GSE17536). Functional enrichment, immune infiltrations, and scRNA-seq analysis were performed to investigate biological processes and the tumor microenvironment (TME). Additionally, functional assays were performed to assess the impact of gene knockdown on COAD cell behavior.
A 3-gene signature (SUSD5, FABP4, CALB2) was identified, demonstrating robust predictive performance for clinical outcomes in COAD patients across multiple cohorts. The signature revealed involvement in critical cancer-related biological processes and showed potential in guiding therapeutic decisions. The bulk RNA-seq and scRNA-seq analysis suggested that LRGs modulates the TME, particularly immune cell populations like mast cells. Knockdown of CALB2 significantly suppressed COAD cell proliferation, invasion, and migration.
This comprehensive analysis identified a lactylation-related signature with significant prognostic and therapeutic implications for COAD. The findings highlight the importance of lactylation in COAD biology and offer novel insights for developing personalized treatment strategies, potentially improving patient outcomes in this prevalent malignancy.
本研究旨在确定一种与乳酰化相关的基因特征，用于预测结肠腺癌（COAD）的预后并指导治疗。我们试图应对由于肿瘤异质性和可变的治疗反应而导致的COAD预后评估方面的挑战。
该研究对来自公共数据库的多组学数据进行了综合生物信息学分析，包括基因表达谱、临床数据和与乳酰化相关的基因（LRG）。应用最小绝对收缩和选择算子（LASSO）回归分析和Cox风险模型来开发一种预后特征。在四个独立的COAD队列（GSE39582、GSE71187、GSE75500和GSE17536）中评估了该特征的预测能力。进行了功能富集、免疫浸润和单细胞RNA测序（scRNA-seq）分析，以研究生物学过程和肿瘤微环境（TME）。此外，进行了功能试验，以评估基因敲低对COAD细胞行为的影响。
确定了一个由3个基因组成的特征（SUSD5、FABP4、CALB2），在多个队列中对COAD患者的临床结局显示出强大的预测性能。该特征揭示了其参与关键的癌症相关生物学过程，并在指导治疗决策方面显示出潜力。批量RNA测序和scRNA-seq分析表明，LRG调节TME，特别是肥大细胞等免疫细胞群体。敲低CALB2可显著抑制COAD细胞的增殖、侵袭和迁移。
这项综合分析确定了一种与乳酰化相关的特征，对COAD具有显著的预后和治疗意义。这些发现突出了乳酰化在COAD生物学中的重要性，并为制定个性化治疗策略提供了新的见解，有可能改善这种常见恶性肿瘤患者的预后。
