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趋化因子家族在结直肠癌中的意义及预后价值

Chemokine family significance and prognostic value in colorectal cancer.

作者信息

Ding Yi, Chen Yinnan, Xie Siyun, Qiu Quanpeng, Guo Xiaolong, Feng Yun, Li Hongxia, Zhu Fang, Liu Yaping

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

出版信息

Front Immunol. 2025 Jan 6;15:1404768. doi: 10.3389/fimmu.2024.1404768. eCollection 2024.

DOI:10.3389/fimmu.2024.1404768
PMID:39835121
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11743568/
Abstract

BACKGROUND

Colorectal cancer (CRC) poses a substantial global health concern, exhibits inconspicuous early symptoms, and is typically diagnosed at advanced stages leading to unfavorable outcomes. The intricate tumor microenvironment plays a crucial role in CRC development and progression, where chemokines contribute significantly. These chemokines exhibit widespread expression within tumor cells, facilitating immune cell infiltration, angiogenesis, and the establishment of distant metastases. The dysregulation of various chemokines in the context of CRC has emerged as a pivotal factor in the disease's pathogenesis.

METHODS

To explore the relationship between chemokine gene expression and CRC patient survival, as well as to clarify their biological roles,We conducted RNA-sequencing (RNA-seq) analysis on a cohort of 88 CRC patients with tumor samples, thereby enabling a detailed exploration of chemokine involvement in CRC. This study was rigorously augmented using comprehensive datasets from The Cancer Genome Atlas (TCGA), ensuring a robust analysis of gene expression patterns associated with clinical outcomes.

RESULTS

Through data analysis, we identified key genes from the chemokine family thought pertinent to CRC outcomes. Consequently, we constructed a novel prognostic model based on the risk score derived from these chemokine expressions. Validation against clinical metadata, executed through immunohistochemistry analysis, affirmed the relevance and accuracy of our model in predicting patient survival.

CONCLUSION

Our findings illuminate the critical role of chemokines in shaping the immune microenvironment of CRC, thereby highlighting potential therapeutic targets for future treatment strategies. Our new prognostic model could provide important information for the development of targeted therapies for CRC, enhancing personalized treatment approaches andultimately improving survival for CRC patients.

摘要

背景

结直肠癌(CRC)是一个重大的全球健康问题,其早期症状不明显,通常在晚期才被诊断出来,导致预后不佳。复杂的肿瘤微环境在CRC的发生和发展中起着关键作用,趋化因子在其中发挥了重要作用。这些趋化因子在肿瘤细胞中广泛表达,促进免疫细胞浸润、血管生成和远处转移的形成。CRC中各种趋化因子的失调已成为该疾病发病机制的关键因素。

方法

为了探索趋化因子基因表达与CRC患者生存之间的关系,并阐明它们的生物学作用,我们对88例患有肿瘤样本的CRC患者进行了RNA测序(RNA-seq)分析,从而能够详细探究趋化因子在CRC中的作用。本研究使用来自癌症基因组图谱(TCGA)的综合数据集进行了严格扩充,以确保对与临床结果相关的基因表达模式进行有力分析。

结果

通过数据分析,我们从趋化因子家族中确定了与CRC结果相关的关键基因。因此,我们基于这些趋化因子表达得出的风险评分构建了一个新的预后模型。通过免疫组织化学分析对临床元数据进行验证,证实了我们的模型在预测患者生存方面的相关性和准确性。

结论

我们的研究结果阐明了趋化因子在塑造CRC免疫微环境中的关键作用,从而突出了未来治疗策略的潜在治疗靶点。我们的新预后模型可为CRC靶向治疗的开发提供重要信息,加强个性化治疗方法,并最终提高CRC患者的生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/d3e1193005f6/fimmu-15-1404768-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/8daef8058d86/fimmu-15-1404768-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/d2c4e942705e/fimmu-15-1404768-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/081b93f88f32/fimmu-15-1404768-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/af1b97ef7984/fimmu-15-1404768-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/22a123811302/fimmu-15-1404768-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/857d6912b503/fimmu-15-1404768-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/f8950f216c4d/fimmu-15-1404768-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/d3e1193005f6/fimmu-15-1404768-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/8daef8058d86/fimmu-15-1404768-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/d2c4e942705e/fimmu-15-1404768-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/081b93f88f32/fimmu-15-1404768-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/af1b97ef7984/fimmu-15-1404768-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/22a123811302/fimmu-15-1404768-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/857d6912b503/fimmu-15-1404768-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/f8950f216c4d/fimmu-15-1404768-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569b/11743568/d3e1193005f6/fimmu-15-1404768-g008.jpg

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Tumor bud-derived CCL5 recruits fibroblasts and promotes colorectal cancer progression via CCR5-SLC25A24 signaling.
肿瘤芽衍生的 CCL5 通过 CCR5-SLC25A24 信号招募成纤维细胞并促进结直肠癌进展。
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CX3CR1 Acts as a Protective Biomarker in the Tumor Microenvironment of Colorectal Cancer.CX3CR1 在结直肠癌肿瘤微环境中作为一种保护性生物标志物。
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Anticancer opportunities at every stage of chemokine function.在趋化因子功能的各个阶段都有抗癌机会。
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