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多维度分析 Gemmatimonas、Rhodothermus 和 Sutterella 对结直肠癌药物和治疗反应的影响。

Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer.

机构信息

Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing, China.

出版信息

Front Cell Infect Microbiol. 2024 Oct 8;14:1457461. doi: 10.3389/fcimb.2024.1457461. eCollection 2024.

Abstract

BACKGROUND

Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer.

OBJECTIVE

This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response.

METHODS

An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined.

RESULTS

A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer.

CONCLUSION

This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.

摘要

背景

结直肠癌是全球第三大常见癌症。尽管有多种治疗方法,但该疾病的复发率和死亡率仍然很高。最近的研究表明,肠道微生物群与结直肠癌的发生、发展、治疗反应和预后密切相关。

目的

本研究旨在整合转录组和微生物组数据,鉴定与不同肠道微生物群相关的结直肠癌亚型,并评估它们在患者生存预后、肿瘤微环境(TME)和药物治疗反应中的作用。

方法

对公共数据库中结直肠癌样本的微生物组数据进行综合分析。在此基础上,鉴定出与患者生存预后密切相关的两种肿瘤亚型(C1 和 C2),并构建风险评分模型。深入分析患者的生存状态、临床参数、免疫评分等特征,并检测各种潜在药物的敏感性。

结果

对结直肠癌患者的微生物组信息进行深入研究,确定了两种主要的肿瘤簇(C1 和 C2),它们在生存结果上存在显著差异。C1 亚型的患者与更好的预后相关,而 C2 亚型的患者具有更高的肠道微生物丰富度和较差的生存预后。利用微生物组数据开发了一种预测模型,可准确预测结直肠癌患者的生存结局。TME 评分提供了高危(类似于 C2 亚型)患者队列风险评估的生物学基础。评估不同亚型对各种潜在药物的敏感性表明,个性化治疗至关重要。进一步分析表明,所开发的风险评分模型在预测患者免疫检查点功能和治疗反应方面具有良好的潜力,这可能对指导结直肠癌患者免疫治疗策略的选择至关重要。

结论

本研究通过对结直肠癌微生物组、免疫微环境和药物敏感性的综合分析,增强了对结直肠癌多维相互作用的理解,为改善未来治疗策略提供了重要的临床指标。研究结果为通过调节微生物群或利用其提供的生物标志物来改善 CRC 患者的治疗反应和长期预后提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a4/11493733/a20ad9b4bba2/fcimb-14-1457461-g001.jpg

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