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基于相对表达排序预测晚期黑色素瘤抗程序性死亡蛋白1免疫治疗的反应

Relative expression orderings based prediction of treatment response to Anti-PD-1 immunotherapy in advanced melanoma.

作者信息

Gao Yaru, Huo Yue, Wang Lingli, Ruan Jiayi, Chen Lanzhen, Li Hongdong, Hong Guini

机构信息

School of Public Health and Health Management, Gannan Medical University, Ganzhou, 341000, China.

School of Medical and Information Engineering, Gannan Medical University, Ganzhou, 341000, China.

出版信息

Sci Rep. 2025 Mar 25;15(1):10235. doi: 10.1038/s41598-025-94931-0.

DOI:10.1038/s41598-025-94931-0
PMID:40133499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11937249/
Abstract

Programmed cell death protein 1 (PD-1) plays a critical role in immune tolerance and evasion within the tumor microenvironment, and anti-PD-1 immunotherapy has shown efficacy in treating advanced melanoma. However, response rates vary significantly among patients, necessitating the identification of reliable biomarkers to predict treatment efficacy. Based on within-sample relative expression orderings, we analyzed RNA sequencing data from melanoma patients to construct a predictive model comprising gene pairs associated with treatment response. The model's performance was validated across multiple independent datasets and assessed for correlations with immune infiltration and survival outcomes. The constructed 15-pair model achieved a prediction accuracy of 100% in training datasets and 89.47% in validation sets. Validation in melanoma patients lacking treatment response data revealed significant differences between predicted responders and non-responders across datasets, with the model being an independent prognostic factor. Increased immune cell infiltration was observed in responders, correlating with higher expression levels of key immune checkpoint genes. The relative expression orderings-based model shows promise as a tool for predicting responses to anti-PD-1 therapy in melanoma patients, supporting personalized treatment strategies.

摘要

程序性细胞死亡蛋白1(PD-1)在肿瘤微环境中的免疫耐受和逃逸中起关键作用,抗PD-1免疫疗法已显示出治疗晚期黑色素瘤的疗效。然而,患者之间的反应率差异很大,因此需要确定可靠的生物标志物来预测治疗效果。基于样本内相对表达顺序,我们分析了黑色素瘤患者的RNA测序数据,以构建一个包含与治疗反应相关基因对的预测模型。该模型的性能在多个独立数据集中得到验证,并评估了与免疫浸润和生存结果的相关性。构建的15对模型在训练数据集中的预测准确率达到100%,在验证集中达到89.47%。在缺乏治疗反应数据的黑色素瘤患者中进行的验证显示,各数据集中预测的反应者和无反应者之间存在显著差异,该模型是一个独立的预后因素。在反应者中观察到免疫细胞浸润增加,这与关键免疫检查点基因的较高表达水平相关。基于相对表达顺序的模型有望成为预测黑色素瘤患者抗PD-1治疗反应的工具,支持个性化治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de59/11937249/be2b21550926/41598_2025_94931_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de59/11937249/48141fb4ef34/41598_2025_94931_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de59/11937249/37c3c539f962/41598_2025_94931_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de59/11937249/be2b21550926/41598_2025_94931_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de59/11937249/48141fb4ef34/41598_2025_94931_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de59/11937249/37c3c539f962/41598_2025_94931_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de59/11937249/be2b21550926/41598_2025_94931_Fig3_HTML.jpg

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本文引用的文献

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磷酸甲羟戊酸激酶产生的 4-乙酰氨基丁酸增加抑制 CD8 T 细胞激活并允许肿瘤免疫逃逸。
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NUP43 promotes PD-L1/nPD-L1/PD-L1 feedback loop via TM4SF1/JAK/STAT3 pathway in colorectal cancer progression and metastatsis.NUP43通过TM4SF1/JAK/STAT3通路促进结直肠癌进展和转移过程中的PD-L1/nPD-L1/PD-L1反馈环。
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