RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Decoding the immune landscape: a comprehensive analysis of immune-associated biomarkers in cervical carcinoma and their implications for immunotherapy strategies.
Decoding the immune landscape: a comprehensive analysis of immune-associated biomarkers in cervical carcinoma and their implications for immunotherapy strategies.
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因此,IRGPI 是一种与 CESC 患者生存及 TIME 状态均密切相关的生物标志物,为 CESC 的免疫治疗策略提供了潜在见解。
宫颈癌是威胁女性健康和生命的常见妇科恶性肿瘤。免疫检查点抑制剂为治疗带来希望;对持续、复发或转移性宫颈癌患者,PD-L1阳性可能提示疗效。PD-L1是有价值的预测标志物,但肿瘤免疫微环境的免疫细胞组成和TIL状态也深刻影响免疫反应及预后,因此需要整合微环境多个方面的生物标志物。本研究基于TCGA宫颈鳞癌和宫颈管腺癌数据建立免疫相关基因预后指数(IRGPI),并以医院队列验证。该指数由EPGN、LCN10和TP73构成,与生存呈显著负相关。IRGPI可预测多种免疫细胞亚群组成,也能反映TIL排斥、功能障碍及PD-1/PD-L1表达。结果提示IRGPI与患者生存和肿瘤免疫微环境状态密切相关,有望用于预后评估及免疫特征表征,并为宫颈癌免疫治疗策略提供参考。
In this study, we have developed an Immune-Associated Gene Prognostic Index (IRGPI) with remarkable prognostic value specifically for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The Cancer Genome Atlas CESC dataset ( n = 305) was meticulously analyzed to pinpoint key immune-related genes via weighted gene co-expression network analysis and differential gene expression assays. Subsequently, we employed Cox regression analysis to construct the IRGPI. Furthermore, the composition of immune cells and TIL status were examined using CIBERSORT and TIDE. Tumor expression of Epigen, LCN10, and P73 were determined with immunohistochemistry.
The resulting IRGPI, composed of EPGN, LCN10, and TP73 genes, displayed a strong negative correlation with patient survival. The discovery was validated with a patient cohort from our hospital. The IRGPI not only predicts the composition of immune cell subtypes such as Macrophages M1, NK cells, Mast cells, Plasma cells, Neutrophils, Dendritic cells, T cells CD8, and T cells CD4 within CESC, but also indicates TIL exclusion, dysfunction, and PD-1 and PD-L1 expression. Therefore, the IRGPI emerges as a promising biomarker not only for prognostic assessment but also for characterizing multiple immune features in CESC. Additionally, our results underscored the significant associations between the IRGPI and immune cell composition, TIL exclusion, and dysfunction, along with PD-1 and PD-L1 expression in the TIME.
Consequently, the IRGPI stands out as a biomarker intimately connected to both the survival and TIME status of CESC patients, offering potential insights into immunotherapy strategies for CESC.
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