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基于可溶性介质相关基因的生物信息学分析构建结直肠癌预后列线图模型并预测免疫特征和免疫治疗反应

The construction of a prognostic nomogram model for colorectal cancer and the prediction of immune characteristics and immune treatment responses based on the bioinformatics analysis of soluble mediator-related genes.

作者信息

Yang Leilei, Yang Xiuying, Fang Chengfeng, Han Jiaju, Ji Zhiqing, Zhang Ruili, Zhou Shenkang

机构信息

Department of Gastrointestinal Surgery, Taizhou Hospital, Wenzhou Medical University, Linhai City, Taizhou City, China.

Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai City, Taizhou City , China.

出版信息

Hum Vaccin Immunother. 2025 Dec;21(1):2555699. doi: 10.1080/21645515.2025.2555699. Epub 2025 Sep 12.

Abstract

Accurate prognosis prediction in colorectal cancer (CRC) is essential for personalized treatment. Soluble mediators are promising predictive biomarkers for evaluating outcomes. We sourced transcriptome data of CRC (COAD+READ) from TCGA and GEO. Soluble mediator-related genes (SMRGs) were identified via GeneCards. Through univariate Cox and Lasso regression analyses, prognosis-related feature genes were determined. A prognostic model was created using multivariate Cox regression, categorizing patients into high-risk (HR) and low-risk (LR) groups based on the median riskscore. KEGG pathway enrichment analysis and GSEA were undertaken on groups. ssGSEA assessed immune cell scores, while ESTIMATE analysis evaluated stromal and immune cell scores along with tumor purity. The CellMiner database identified potential drugs for HR patients. Pearson correlation analysis revealed the relationship between mismatch repair (MMR) genes and model genes. We identified 10 SMRGs. Pearson correlation analysis indicated positive correlations among these genes. GO analysis showed that most feature genes were linked to binding functions. KEGG analysis revealed that the HR group was enriched in pathways like Basal cell carcinoma and Glycosaminoglycan biosynthesis. The ssGSEA indicated higher immune cell scores in the LR group, alongside lower stromal scores. LR group also exhibited a lower TIDE score and higher immunophenoscore. Drug sensitivity analysis suggested PF-4708671, PI-103, and XAV939 as potential treatments for HR patients. There was significant correlation between model gene and MMR genes. The CRC prognostic model based on SMRGs effectively predicts patient prognosis and guides treatment strategies.

摘要

结直肠癌(CRC)的准确预后预测对于个性化治疗至关重要。可溶性介质是评估预后的有前景的预测生物标志物。我们从TCGA和GEO获取了CRC(COAD+READ)的转录组数据。通过GeneCards鉴定了可溶性介质相关基因(SMRG)。通过单变量Cox和Lasso回归分析,确定了与预后相关的特征基因。使用多变量Cox回归创建了一个预后模型,根据中位风险评分将患者分为高风险(HR)和低风险(LR)组。对各组进行了KEGG通路富集分析和GSEA。ssGSEA评估免疫细胞评分,而ESTIMATE分析评估基质和免疫细胞评分以及肿瘤纯度。CellMiner数据库为HR患者确定了潜在药物。Pearson相关性分析揭示了错配修复(MMR)基因与模型基因之间的关系。我们鉴定了10个SMRG。Pearson相关性分析表明这些基因之间呈正相关。GO分析表明,大多数特征基因与结合功能有关。KEGG分析显示,HR组在基底细胞癌和糖胺聚糖生物合成等通路中富集。ssGSEA表明LR组的免疫细胞评分较高,同时基质评分较低。LR组还表现出较低的TIDE评分和较高的免疫表型评分。药物敏感性分析表明PF-4708671、PI-103和XAV939是HR患者的潜在治疗药物。模型基因与MMR基因之间存在显著相关性。基于SMRG的CRC预后模型有效地预测了患者的预后并指导了治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab3/12439576/f08f93df2f20/KHVI_A_2555699_F0001_OC.jpg

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