Identification and validation of the prognostic signature of a novel demethylation-related gene associated with the clinical features of colon cancer.

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2024-09-30 Epub Date: 2024-07-29 DOI:10.1016/j.intimp.2024.112798

Kuo Kang, Heyuan Huang, Zihua Chen

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Abstract

Background: The aim of this study was to construct a prognostic model of colon cancer based on demethylation-related genes. An in-depth understanding of the relationship between the set of demethylated genes and colon cancer not only assists in revealing the pathogenesis of colon cancer but also provides strong support for future therapeutic strategies and individualized medicine.

Methods: Data were obtained from the TCGA database and the GEO-GSE39582 cohort. A risk score model for demethylation-related genes was developed using univariate Cox regression analysis and LASSO regression analysis. The accuracy and reliability of the model were confirmed using K-M survival analysis and ROC curve analysis. Additionally, a nomogram was created by integrating the risk score and clinicopathological variables. Finally, the biological function of the RCOR2 gene was verified by performing qPCR, MTT, colony formation, Transwell, and subcutaneous tumor formation assays in nude mice.

Results: We constructed a risk score model containing 30 demethylation-related genes for predicting the survival risk of patients with colon cancer. COAD patients were categorized into high-risk and low-risk groups, and Kaplan-Meier (KM) curve analysis revealed that the high-risk group was associated with a worse prognosis. Univariate and multivariate Cox regression analyses validated the risk score as an independent prognostic factor for COAD. We also analyzed the differences in the sensitivity to nine chemotherapeutic agents and small molecule targeted drugs between the high-risk and low-risk groups. Moreover, we performed experiments in COAD cell lines and nude mice to verify that RCOR2 was differentially expressed between tumor tissues and normal tissues and that high RCOR2 expression promoted a malignant phenotype of colon cancer.

Conclusion: This study demonstrated the potential roles of demethylation-related genes in colon cancer by conducting a comprehensive analysis and constructing a risk score. These findings also highlight the ability of these genes to indicate patient prognosis and tumor immune microenvironment. Furthermore, this study provides a reliable predictive tool that can assist in guiding the treatment and management of colon cancer patients.

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鉴定和验证与结肠癌临床特征相关的新型去甲基化相关基因的预后特征。

研究背景本研究旨在构建基于去甲基化相关基因的结肠癌预后模型。深入了解去甲基化基因集与结肠癌之间的关系不仅有助于揭示结肠癌的发病机制，还能为未来的治疗策略和个体化医疗提供有力支持：方法：数据来自TCGA数据库和GEO-GSE39582队列。方法：数据来自 TCGA 数据库和 GEO-GSE39582 队列，利用单变量 Cox 回归分析和 LASSO 回归分析建立了去甲基化相关基因的风险评分模型。利用 K-M 生存分析和 ROC 曲线分析确认了模型的准确性和可靠性。此外，还通过整合风险评分和临床病理变量建立了一个提名图。最后，通过在裸鼠体内进行 qPCR、MTT、集落形成、Transwell 和皮下肿瘤形成试验，验证了 RCOR2 基因的生物学功能：我们构建了一个包含 30 个去甲基化相关基因的风险评分模型，用于预测结肠癌患者的生存风险。我们将 COAD 患者分为高风险组和低风险组，Kaplan-Meier（KM）曲线分析表明，高风险组患者的预后较差。单变量和多变量 Cox 回归分析验证了风险评分是 COAD 的独立预后因素。我们还分析了高危组和低危组对九种化疗药物和小分子靶向药物敏感性的差异。此外，我们还在 COAD 细胞系和裸鼠中进行了实验，验证了 RCOR2 在肿瘤组织和正常组织中的不同表达，以及 RCOR2 的高表达会促进结肠癌恶性表型的形成：本研究通过全面分析和构建风险评分，证明了去甲基化相关基因在结肠癌中的潜在作用。这些发现还强调了这些基因指示患者预后和肿瘤免疫微环境的能力。此外，这项研究还提供了一种可靠的预测工具，有助于指导结肠癌患者的治疗和管理。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.