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:In-depth analysis of prognostic markers associated with the tumor immune microenvironment and genetic mutations in breast cancer based on an NK cell-related risk model.
In-depth analysis of prognostic markers associated with the tumor immune microenvironment and genetic mutations in breast cancer based on an NK cell-related risk model.
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自然杀伤(NK)细胞群体之所以独特,是因为它由能够检测并消灭肿瘤和病毒感染细胞的固有淋巴细胞组成。本研究旨在基于NK细胞相关基因(NKRGs)识别乳腺癌(BRCA)的一种新的预后信号。从癌症基因组图谱(TCGA)和基因表达数据库(GEO)中收集了多种测序和基因突变数据以及临床信息。进行了COX回归和最小绝对收缩和选择算子(LASSO)Cox回归分析以识别预后基因。
此外,还进行了免疫相关分析,以评估免疫微环境与聚类和风险模型之间的关联。进行了Edu实验、集落形成实验、伤口愈合实验和transwell实验,以评估细胞增殖和侵袭能力。构建了一个基于4-NKRG的预后模型。高风险组患者在TCGA和GSE42568中与较差的OS相关。
此外,构建了一个列线图,以更好地预测BRCA患者的预后。最后,发现IFNE的过表达可以抑制BRCA细胞的增殖和侵袭能力,这可能是一个有前景的BRCA患者生物标志物。
因此,我们开发了一种新的4-NKRG信号和列线图,能够预测BRCA患者的预后。此外,该模型与免疫微环境密切相关,为未来癌症治疗开辟了新的治疗途径。
The natural killer (NK) cell population is unique because it consists of innate lymphocytes capable of detecting and eliminating tumors and virus-infected cells. This research aims to identify a new prognostic signal in breast cancer (BRCA) based on NK-cell-related genes (NKRGs).
A variety of sequencing and gene mutation data, along with clinical information, were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Database (GEO). COX regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were conducted to identify prognostic genes.
In addition, the immune-related analysis was performed to evaluate the association between the immune microenvironment and clusters and risk model. The Edu assay, colony assay, wound healing assay, and transwell assay were performed to evaluate the cell proliferative and invasive abilities. A 4-NKRG-based prognostic model was constructed. Patients in high-risk groups were associated with poorer OS in TCGA and GSE42568.
Further, a nomogram was constructed for better prediction of the prognosis of patients with BRCA.
Finally, it was discovered that the over-expression of IFNE could suppress the proliferative and invasive abilities of BRCA cells, which might be a promising biomarker for patients with BRCA. As a result, we developed a novel 4-NKRG signal and nomogram capable of predicting the prognosis of patients with BRCA.
Additionally, this model was closely associated with the immune microenvironment, which opened new therapeutic avenues for the treatment of cancer in the future.
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