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:Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma.
Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma.
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肺腺癌(LUAD)的异质性表明,靶向治疗和免疫治疗可能并非对所有患者都有效。探索不同基因突变的免疫景观特征可能提供新的视角。
在本研究中,我们从癌症基因组图谱中获取了LUAD样本。通过应用ESTIMATE和ssGSEA,发现KRAS突变组与较低的免疫浸润、较低的免疫检查点表达相关,尤其是B细胞、CD8+ T细胞、树突状细胞、NK 细胞和巨噬细胞的丰度较低,而中性粒细胞和内皮细胞的丰度较高。通过ssGSEA,我们发现KRAS突变组中抗原呈递细胞共抑制和共刺激过程受到抑制,细胞溶解活性和人类白细胞抗原分子下调。通过基因功能富集分析,KRAS突变与抗原呈递和加工、细胞毒性淋巴细胞活性、细胞溶解活性以及细胞因子相互作用信号通路呈负相关。
最后,我们识别出24个免疫相关基因,建立了一个具有优异预后预测能力的免疫相关基因特征,其1年、3年和5年AUC分别为0.893、0.986和0.999。
我们的研究结果阐明了KRAS突变组的免疫景观特征,并成功在LUAD中基于免疫相关基因建立了一个预后特征。
The heterogeneity of lung adenocarcinoma (LUAD) indicated that target therapies and immunotherapies may not be effective in all patients. The exploration of the feature of the immune landscape of different gene mutations may provide novel perspectives. In this study, we obtained LUAD samples from The Cancer Genome Atlas. By applying ESTIMATE and ssGSEA, KRAS-mutated group was discovered to be associated with lower immune infiltration, lower expression of immune checkpoints, especially, a lower abundance of B cell, CD8+ T cell, dendritic cell, natural killer cell, and macrophage, higher abundance of neutrophil and endothelial cell.
Through ssGSEA, we found that the process of antigen-presenting cell co-inhibition and co-stimulation were inhibited, cytolytic activity and human leukocyte antigen molecules were downregulated in the KRAS-mutated group. And KRAS mutation is negatively related to antigen presentation and procession, cytotoxic lymphocyte activity, cytolytic activities, and cytokine interaction signaling pathway via gene function enrichment analysis.
Finally, 24 immune-related genes were identified to establish an immune-related gene signature with excellent prognostic prediction capacity, whose 1-, 3- and 5-year AUCs were 0. 893, 0. 986, and 0. 999.
Our findings elucidate the features of the immune landscape of KRAS-mutated groups and successfully established a prognostic signature on the basis of immune-related genes in LUAD.
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