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:Prognostic implication of novel immune-related signature in breast cancer.
Prognostic implication of novel immune-related signature in breast cancer.
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检查点抑制剂治疗已变得越来越重要,并已被认可为乳腺癌的一种治疗方案。但获益仅限于一小部分患者。我们旨在基于免疫基因开发一种改进的特征,以检测免疫治疗的潜在获益。初步从癌症基因组图谱中提取乳腺癌患者的基因表达数据进行分析。从差异表达基因与免疫相关基因的交互作用中筛选出10个基因,以开发生存特征。
我们通过基因集富集分析、免疫浸润、检查点分子表达和免疫表型评分对高风险组和低风险组进行比较。从差异表达基因与免疫相关基因的交互作用中提取出10个基因。免疫风险评分基于枢纽基因的Cox回归系数确定,并用GSE96058数据集进行验证。与低风险组相比,高风险组中免疫细胞浸润更高,包括CD8 + T细胞、浆细胞、滤泡辅助T细胞、CD4 + 记忆T细胞、M1巨噬细胞、调节性T细胞和静息NK细胞。与低风险组相比,高风险组中检查点分子,包括CTLA-4、PD-L1、TIM-3、VISTA、ICOS、PD-1和PD-L2的表达水平显著更低。作为免疫检查点治疗反应的替代指标,免疫表型评分在高风险组中观察到显著更低。这个10基因预后特征可以识别患者的生存情况,并与免疫检查点抑制剂治疗的生物标志物相关,这可能指导临床实践中的精准治疗决策。
Checkpoint inhibitor therapy has become increasingly important and has been endorsed as a treatment regimen in breast cancer.
But benefits were limited to a small proportion of patients.
We aimed to develop an improved signature on the basis of immune genes for detection of potential benefit from immunotherapy. Gene expression data of patients with breast cancer initially extracted from The Cancer Genome Atlas were analyzed. Ten genes were selected from the interaction of differentially expressed genes as well as immune-related genes to develop a survival signature.
We compared the high-risk and low-risk groups by gene set enrichment analysis, immune infiltration, checkpoint molecule expression and immunophenoscore. Ten genes were extracted from interactions of differentially expressed and immune-related genes. The immune risk score was determined on the basis of the Cox regression coefficient of hub genes and validated with the GSE96058 dataset. Immune cell infiltrates, including CD8 + T cells, plasma cells, follicular helper T cells, CD4 + memory T cells, M1 macrophages, regulatory T cells and resting NK cells, were more highly infiltrated in the high-risk group as compared to the low-risk group.
Checkpoint molecules, including CTLA-4, PD-L1, TIM-3, VISTA, ICOS, PD-1, and PD-L2, were expressed at markedly lower levels in the high-risk group as compared to the low-risk group. Immunophenoscores, as a surrogate of response to immune checkpoint therapy, was observed significant lower in the high-risk group. The 10-gene prognostic signature could identify patients' survival and was correlated with the biomarkers of immune checkpoint inhibitor therapy, which may guide precise therapeutic decisions in clinical practice.
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