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结直肠癌中的免疫基因特征与预后:来自单样本基因集富集分析(ssGSEA)分型的见解

Immune gene features and prognosis in colorectal cancer: insights from ssGSEA typing.

作者信息

Huang Anwen, Wu Jinxiu, Wang Jiakuan, Jiao Chengwen, Yang Yunfei, Xiao Huaiwen, Yao Li

机构信息

Department of Hepatopancreatobiliary Surgery, Shanghai Punan Hospital, Shanghai, 200125, China.

Department of General Surgery, Shanghai Punan Hospital, Shanghai, 200125, China.

出版信息

Discov Oncol. 2025 Feb 8;16(1):139. doi: 10.1007/s12672-025-01928-2.

Abstract

BACKGROUND

Colorectal cancer (CRC) is a molecularly heterogeneous disease, and its treatment and prognosis vary greatly among subgroups. Therefore, it is necessary to identify prognostic factors associated with the biological heterogeneity of CRC in order to improve patients' survival expectations.

METHODS

We obtained and merged RNA-Seq data along with clinical details for colorectal cancer (CRC) from The Cancer Genome Atlas (TCGA) repository, and then performed immunocluster typing on all CRC specimens. We conducted differential expression gene (DEG) analysis, gene set enrichment analysis (GSEA), and tumor microenvironment (TME) analysis on CRC samples that were divided into high and low Immunity categories. Moreover, we pinpointed prognostic genes from immune-related gene (IRGs) sets, developed a prognostic risk model, and executed survival analysis, receiver operating characteristic (ROC) curve analysis, and independent prognostic analysis. Additionally, we assessed the risk for patients categorized into high- and low-risk groups based on the model. Lastly, we created a Nomogram to customize the prediction of survival outcomes in CRC patients.

RESULTS

CRC samples were divided into high and low Immunity groups based on the median value of the immunity score. Between the two groups, a total of 1550 DEGs were identified and 395 differentially expressed immune-related genes (DE-IRGs) were identified by intersection with 2483 IRGs. The DE-IRGs of the high Immunity group were dominated by Cytokine receptor interactions, chemokine signaling pathways and immune cell-mediated cytotoxicity, and molecule function of immune effector process. TME analysis showed that most of the 27 immune cells and functions were highly enriched in high Immunity group, whose Immune Score, Stromal Score and ESTIMATE Score were significantly higher. Subsequently, a prognostic risk model of CRC was constructed based on 12 prognostic genes, and the accuracy and reliability of the model prediction were verified. Finally, Nomogram enabled accurate individual prediction of the survival prognosis of CRC patients.

CONCLUSIONS

Our study develops an immune-related prognostic model and Nomogram that reliably predicts survival outcomes in CRC patients and enhances understanding of the tumor immunity and molecular mechanisms of CRC.

摘要

背景

结直肠癌(CRC)是一种分子异质性疾病,其治疗和预后在不同亚组之间差异很大。因此,有必要确定与CRC生物学异质性相关的预后因素,以提高患者的生存预期。

方法

我们从癌症基因组图谱(TCGA)数据库中获取并合并了结直肠癌(CRC)的RNA测序数据以及临床细节,然后对所有CRC标本进行免疫聚类分型。我们对分为高免疫组和低免疫组的CRC样本进行了差异表达基因(DEG)分析、基因集富集分析(GSEA)和肿瘤微环境(TME)分析。此外,我们从免疫相关基因(IRG)集中确定了预后基因,建立了预后风险模型,并进行了生存分析、受试者工作特征(ROC)曲线分析和独立预后分析。此外,我们根据该模型评估了分为高风险组和低风险组的患者的风险。最后,我们创建了一个列线图,以定制CRC患者生存结果的预测。

结果

根据免疫评分的中位数,将CRC样本分为高免疫组和低免疫组。两组之间,共鉴定出1550个DEG,并通过与2483个IRG交叉鉴定出395个差异表达的免疫相关基因(DE-IRG)。高免疫组的DE-IRG主要由细胞因子受体相互作用、趋化因子信号通路和免疫细胞介导的细胞毒性以及免疫效应过程的分子功能主导。TME分析表明,27种免疫细胞和功能中的大多数在高免疫组中高度富集,其免疫评分、基质评分和ESTIMATE评分显著更高。随后,基于12个预后基因构建了CRC的预后风险模型,并验证了模型预测的准确性和可靠性。最后,列线图能够准确地对CRC患者的生存预后进行个体预测。

结论

我们的研究开发了一种免疫相关的预后模型和列线图,能够可靠地预测CRC患者的生存结果,并增强了对CRC肿瘤免疫和分子机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/661e/11807041/bb8a4492dd94/12672_2025_1928_Fig1_HTML.jpg

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