Cai Ruyun, Hong Zhonghua, Yin Hezhai, Chen Huilin, Qin Mengting, Huang Yihong
Department of Surgery, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Jiaxing, China.
Transl Cancer Res. 2025 Feb 28;14(2):1053-1069. doi: 10.21037/tcr-24-1511. Epub 2025 Feb 26.
Immunotherapy is playing an increasing role in the treatment of various cancers. However, its application in rectal cancer is very limited as only microsatellite-unstable bowel cancers with defective mismatch repair are found to benefit. The majority of rectal cancers belong to the microsatellite-stable phenotype. Therefore, the aim of this study is to explore immune-related genes within the tumor microenvironment of rectal cancer, with the objective of discovering novel biomarkers and therapeutic targets for rectal cancer, and to establish a new prognostic prediction model for rectal cancer based on these immune-related genes.
The data in The Cancer Genome Atlas (TCGA) database were processed using the Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm to obtain differently expressed genes (DEGs). Then the DEGs were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genomes (KEGG), Reactome function enrichment analysis, and protein-protein interaction (PPI) analysis to screen the core genes, which were utilized to compute the risk scores of individual patients. Finally, combining risk scores and clinical characteristics, a new prognostic prediction model was established by univariate and multivariate Cox analyses, and the prognostic model was validated by the Gene Expression Omnibus (GEO) database.
The study finally identified four core genes (, , , and ), and immune cell infiltration analyses of the four core genes showed that their expression levels were positively correlated with the distribution of various immune cells. The 4-gene risk score categorized rectal cancer patients into high-risk and low-risk groups, and the results showed that the low-risk group had a stronger correlation with the immune response and had a better prognosis. A prognostic model was developed by integrating risk scores and clinical characteristics and showed a strong predictive effect.
In patients with rectal cancer, , , , and are immune-related core genes, and low expression of each gene is associated with poor clinical prognosis. The risk score obtained on their basis is independent prognostic factors for rectal cancer, suggesting that the four core genes may provide a foundation for the development of new prognostic biomarkers for rectal cancer and the study of immunotherapy.
免疫疗法在各种癌症的治疗中发挥着越来越重要的作用。然而，其在直肠癌中的应用非常有限，因为仅发现微卫星不稳定且错配修复缺陷的肠癌患者能从中获益。大多数直肠癌属于微卫星稳定表型。因此，本研究旨在探索直肠癌肿瘤微环境中的免疫相关基因，以期发现新的生物标志物和治疗靶点，并基于这些免疫相关基因建立一种新的直肠癌预后预测模型。
使用肿瘤组织基因表达数据估算基质细胞和免疫细胞（ESTIMATE）算法处理癌症基因组图谱（TCGA）数据库中的数据，以获得差异表达基因（DEG）。然后通过基因本体论（GO）、京都基因与基因组百科全书（KEGG）、Reactome功能富集分析以及蛋白质-蛋白质相互作用（PPI）分析对DEG进行分析，以筛选核心基因，并利用这些核心基因计算个体患者的风险评分。最后，结合风险评分和临床特征，通过单因素和多因素Cox分析建立新的预后预测模型，并通过基因表达综合数据库（GEO）进行验证。
本研究最终确定了四个核心基因（ 、 、 和 ），对这四个核心基因的免疫细胞浸润分析表明，它们的表达水平与各种免疫细胞的分布呈正相关。基于这四个基因的风险评分将直肠癌患者分为高风险组和低风险组，结果显示低风险组与免疫反应的相关性更强，预后更好。通过整合风险评分和临床特征建立了一种预后模型，该模型显示出强大的预测效果。
在直肠癌患者中， 、 、 和 是免疫相关核心基因，每个基因的低表达均与不良临床预后相关。基于它们获得的风险评分是直肠癌的独立预后因素，这表明这四个核心基因可能为开发新的直肠癌预后生物标志物及免疫治疗研究提供基础。
