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:Identification of testicular cancer immune infiltrates and novel immune cell subtypes.
Identification of testicular cancer immune infiltrates and novel immune cell subtypes.
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睾丸生殖细胞肿瘤(TGCT)是睾丸癌最常见的类型,占90-95%的病例,是年轻成年男性中最常见的实体恶性肿瘤。免疫浸润在肿瘤中发挥重要的调控作用,但其在TGCT中的作用仍不清楚。分子分型是提供精准个体化治疗和避免不必要毒性反应的一种有前景的方法。
本研究探讨了TGCT的免疫浸润、关键生物标志物和免疫分型。在GSE3218中,鉴定出24个差异表达的免疫基因(immDEGs)。利用这些基因开发了一个由六个immDEGs组成的新风险特征。高风险组的个体总生存期(OS)较差(风险比为4.61,P值<0.001)。
我们在纯精原细胞瘤和混合型TGCT类型中验证了六-immDEGs风险特征。使用consensusclusterplus鉴定出两种不同的免疫模式(Cluster 1和Cluster 2),与Cluster 2相比,Cluster 1的OS较差(风险比为2.56;P<0.001)。Cluster 1患者的初始B细胞、记忆B细胞、浆细胞、初始CD4 T细胞、gamma delta T细胞和活化树突状细胞均显著低于Cluster 2患者。与WNT信号通路、TGF-信号通路、抗原加工和呈递以及NK细胞介导的细胞毒性相关的基因与TGCT相关。STC1在TGCT组织中升高,其高表达显示TGCT的晚期临床病理特征和不良预后。我们的发现可能有助于增加对TGCT发生和进展的理解。
Testicular germ cell tumors (TGCT) are the most common type of testicular cancer, comprising 90-95% of cases and representing the most prevalent solid malignancy in young adult men. Immune infiltrates play important regulatory roles in tumors, but their role in TGCT remains unclear. Molecular subtyping is a promising way to provide precisely personalized treatment and avoid unnecessary toxicities.
This study investigated immune infiltrates, key biomarkers, and immune subtyping of TGCT. In GSE3218, 24 differentially expressed immune genes (immDEGs) were identified. A new risk signature consisting of six immDEGs was developed using these genes. Individuals in the high-risk group had poor overall survival (OS; hazard ratio of 4. 61 and P-value < 0. 001).
We validated the six-immDEGs risk signature in pure seminoma and mixed TGCT types. Two distinct immune patterns (Cluster 1 and Cluster 2) were identified using the consensusclusterplus, and Cluster 1 possessed an unfavorable OS compared with Cluster 2 (hazard ratio, 2. 56; P < 0. 001). Cluster 1 patients had significantly lower naive B cells, memory B cells, plasma cells, naive CD4 T cells, gamma delta T cells, and activated dendritic cells than Cluster 2 patients.
Genes relating to the WNT signaling pathway, TGF- signaling pathway, antigen processing and presentation, and NK cell-mediated cytotoxicity were associated with TGCT. STC1 was elevated in TGCT tissues, and its high expression showed advanced clinicopathological characteristics and poor prognosis of TGCT.
Our findings may contribute to an increased understanding of the onset and progression of TGCT.
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