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:DIAPH3 is a multifaceted prognostic biomarker that links immunotherapy response to tumor microenvironment in prostate cancer.
DIAPH3 is a multifaceted prognostic biomarker that links immunotherapy response to tumor microenvironment in prostate cancer.
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DIAPH3 是 PCa 中一个稳健的预后生物标志物,与不良预后、免疫浸润和治疗反应相关。DIAPH3 高表达与侵袭性肿瘤进展和较差的生存结局相关,凸显了其在预后建模和治疗选择中的价值。
系统研究DIAPH3在前列腺癌(PCa)中的预后价值,并探索其在连接免疫治疗反应与肿瘤微环境重塑中的潜在作用。
我们分析了TCGA-PRAD、Stockholm、Moffitt、UK和银川队列。比较了肿瘤与邻近组织之间DIAPH3的表达。进行了Kaplan–Meier和多变量Cox分析以评估BCRFS和PFS。使用TIDE和IPS分析免疫治疗反应。分析了基因表达、体细胞突变和免疫微环境状态。
高DIAPH3表达与不良预后相关,并且是BCRFS、PFS和RFS的独立预测因子。功能分析显示其参与细胞周期调控和IL-17信号通路。DIAPH3升高与免疫浸润改变相关,包括Th2淋巴细胞增加以及NK细胞和pDCs减少。DIAPH3表达与免疫治疗反应相关,并在泛癌队列中得到验证。药物敏感性分析显示,PI3K抑制剂在DIAPH3低表达肿瘤中更有效,而PARP抑制剂在DIAPH3高表达肿瘤中更有效。
To systematically investigate the prognostic value of DIAPH3 in prostate cancer (PCa) and explore its potential role in linking immunotherapy response and tumor microenvironment remodeling.
We analyzed TCGA-PRAD, Stockholm, Moffitt, UK, and Yinchuan cohorts. DIAPH3 expression was compared between tumor and adjacent tissues. Kaplan–Meier and multivariate Cox analyses were conducted to assess BCRFS and PFS. Immunotherapy response was analyzed using TIDE and IPS. Gene expression, somatic mutations, and immune microenvironment status were analyzed.
High DIAPH3 expression correlates with poor prognosis and is an independent predictor of BCRFS, PFS, and RFS. Functional analyses show its involvement in cell cycle regulation and IL-17 signaling. Elevated DIAPH3 correlates with altered immune infiltration, including increased Th2 lymphocytes and decreased NK cells and pDCs. DIAPH3 expression associates with immunotherapy response, validated in a pan-cancer cohort. Drug sensitivity analysis revealed PI3K inhibitors are more effective in low DIAPH3 tumors, while PARP inhibitors are more effective in high DIAPH3 tumors.
DIAPH3 is a robust prognostic biomarker in PCa, linked to poor prognosis, immune infiltration, and therapeutic response. High DIAPH3 expression correlates with aggressive tumor progression and poor survival outcomes, highlighting its value for prognostic modeling and therapy selection.
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