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:Multi-omics analysis of zinc finger protein 683 as a prognostic biomarker for immune infiltration in clear cell renal cell carcinoma.
Multi-omics analysis of zinc finger protein 683 as a prognostic biomarker for immune infiltration in clear cell renal cell carcinoma.
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我们的研究确定 ZNF683 是 ccRCC 中一个重要的预后生物标志物,并强调了其与免疫细胞浸润的相关性。这些发现表明,ZNF683 可能在 ccRCC 进展和免疫治疗反应中发挥关键作用,值得进一步研究其作为治疗靶点的潜力。
锌指蛋白683(ZNF683)的异常表达与多种癌症有关,但其在透明细胞肾细胞癌(ccRCC)中的作用仍未得到充分探索。了解ZNF683在ccRCC中的预后意义及其与肿瘤浸润免疫细胞的相关性,可能有助于揭示其作为治疗靶点的潜力。
我们使用癌症基因组图谱(TCGA)、肿瘤免疫评估资源(TIMER)、UALCAN、基因表达谱交互分析(GEPIA)和Kaplan-Meier(KM)绘图仪等数据库评估了ZNF683的表达、其与临床病理变量的相关性以及临床结局。此外,采用定量逆转录聚合酶链反应(qRT-PCR)评估肾癌组织中ZNF683的转录表达。我们综合分析了多个数据库,包括TIMER、GEPIA、TISIDB、ESTIMATE算法和CIBERSORT算法,以确定ZNF683与ccRCC中肿瘤浸润免疫细胞之间的相关性。
我们的分析显示,与正常组织相比,ccRCC组织中ZNF683 mRNA水平显著升高。根据人类蛋白质图谱(HPA)所示,ZNF683蛋白在癌症组织中高表达,尤其是在肾肿瘤细胞中。值得注意的是,ZNF683表达升高与ccRCC中CD8 + T细胞、B细胞、巨噬细胞、Treg细胞、NK细胞和树突状细胞的浸润显著相关。生物信息学分析表明,ZNF683表达与包括PD-1在内的多个免疫检查点强相关。这种关联提示ZNF683可能影响ccRCC免疫治疗的疗效。ZNF683高表达的患者对免疫治疗的敏感性降低。
The abnormal expression of Zinc Finger Protein 683 (ZNF683) has been implicated in various cancers, yet its role in clear cell renal cell carcinoma (ccRCC) remains underexplored. Understanding the prognostic significance of ZNF683 and its correlation with tumor-infiltrating immune cells in ccRCC could offer insights into its potential as a therapeutic target.
We assessed the expression of ZNF683, its correlation with clinical pathological variables, and clinical outcomes using databases such as The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), UALCAN, Gene Expression Profiling Interaction Analysis (GEPIA), and Kaplan-Meier (KM) plotter. Additionally, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate ZNF683 transcriptional expression in renal cancer tissues. A comprehensive analysis of multiple databases, including TIMER, GEPIA, TISIDB, the ESTIMATE algorithm, and the CIBERSORT algorithm, was conducted to determine the correlation between ZNF683 and tumor-infiltrating immune cells in ccRCC.
Our analysis revealed that ZNF683 mRNA levels were significantly elevated in ccRCC tissues compared to normal tissues. ZNF683 protein was highly expressed in cancer tissues, particularly in renal tumor cells, as indicated by the Human Protein Atlas (HPA). Notably, increased ZNF683 expression was significantly associated with the infiltration of CD8 + T cells, B cells, macrophages, Treg cells, NK cells, and dendritic cells in ccRCC. Bioinformatics analyses demonstrated a strong correlation between ZNF683 expression and several immune checkpoints, including PD-1. This association suggests that ZNF683 might impact the efficacy of immunotherapy in ccRCC. Patients with high ZNF683 expression exhibited reduced sensitivity to immunotherapy.
Our study identifies ZNF683 as a significant prognostic biomarker in ccRCC and highlights its correlation with immune cell infiltration. These findings suggest that ZNF683 could play a crucial role in ccRCC progression and response to immunotherapy, warranting further investigation into its potential as a therapeutic target.
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