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全面分析 CCL5 在泛癌预后和免疫治疗中的潜在生物学意义。

Comprehensive analysis of the potential biological significance of CCL5 in pan-cancer prognosis and immunotherapy.

机构信息

Department of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, China.

The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China.

出版信息

Sci Rep. 2024 Sep 27;14(1):22138. doi: 10.1038/s41598-024-73251-9.

Abstract

C-C chemokine ligand 5 (CCL5) plays a crucial role in the advancement of human cancer. Nevertheless, little is known about the multi-omics characterisation of CCL5 and its significance for the immune microenvironment and prognosis of tumor patients. The basal expression levels of the CCL5 gene in normal human tissues, aberrant expression in disease, genomic alterations, prognostic roles, pathway enrichment, immune microenvironment, association with immune checkpoints, drug sensitivity, and the ability to predict patients' immunotherapeutic response to immune checkpoint inhibitors (ICIs) and small molecule drugs were all thoroughly analyzed using data gathered from 33 cancers. Lastly, we were able to validate CCL5's involvement in renal clear cell carcinoma by experimental means. We discovered that CCL5 has distinct expression patterns and a diagnostic biomarker significance in cancer. Furthermore, we discovered that CCL5 is essential for both the tumor microenvironment and pan-cancer. TMB and MSI are two frequent immunological checkpoints that are significantly correlated with CCL5, and patients who express high levels of CCL5 have stronger immunotherapeutic response and a better prognosis after immunotherapy. Eventually, molecular docking was used to find small molecule inhibitors that can specifically target CCL5. Ultimately, it was shown that CCL5 knockdown impeded renal clear cell carcinoma cells' ability to proliferate and invade. Our findings demonstrate the significant potential of CCL5 as an immunotherapeutic response biomarker and prognostic indicator, which may pave the way for more studies on the mechanism of tumor infiltration and CCL5's potential therapeutic applications in cancer.

摘要

C-C 趋化因子配体 5(CCL5)在人类癌症的进展中起着至关重要的作用。然而,人们对 CCL5 的多组学特征及其对肿瘤患者免疫微环境和预后的意义知之甚少。使用从 33 种癌症中收集的数据,全面分析了 CCL5 基因在正常人体组织中的基础表达水平、疾病中的异常表达、基因组改变、预后作用、途径富集、免疫微环境、与免疫检查点的关联、药物敏感性以及预测患者对免疫检查点抑制剂(ICIs)和小分子药物免疫治疗反应的能力。最后,我们通过实验手段验证了 CCL5 在肾透明细胞癌中的参与。我们发现 CCL5 在癌症中有不同的表达模式和诊断生物标志物意义。此外,我们发现 CCL5 对肿瘤微环境和泛癌都是必不可少的。TMB 和 MSI 是两个经常出现的免疫检查点,与 CCL5 显著相关,表达高水平 CCL5 的患者在免疫治疗后具有更强的免疫治疗反应和更好的预后。最终,通过分子对接找到了可以特异性靶向 CCL5 的小分子抑制剂。最终表明,CCL5 敲低抑制了肾透明细胞癌细胞的增殖和侵袭能力。我们的研究结果表明,CCL5 作为免疫治疗反应的生物标志物和预后指标具有重要的潜力,这可能为研究肿瘤浸润的机制和 CCL5 在癌症中的潜在治疗应用铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21a9/11437205/42d6ef67cd9b/41598_2024_73251_Fig1_HTML.jpg

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