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:UCN-Centric Prognostic Model for Predicting Overall Survival and Immune Response in Colorectal Cancer.
UCN-Centric Prognostic Model for Predicting Overall Survival and Immune Response in Colorectal Cancer.
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结直肠癌(CRC)是一种常见的恶性肿瘤,全球发病率位居第三,死亡率位居第二。尽管结肠镜检查等筛查方法取得了进展,但由于缺乏可靠的生物标志物,CRC 的准确诊断仍然具有挑战性。
本研究旨在开发一个稳健的预后模型,以精确预测 CRC 的结局。通过对癌症基因组图谱(TCGA)数据采用加权共表达网络分析(WGCNA)和 Cox 回归分析,我们鉴定出一组与患者生存密切相关的 12 个基因。该基因组合有助于准确预测 CRC 的结局,并通过外部验证队列 GSE17536 得到了验证。
我们利用 CRC 患者的单细胞转录组数据和免疫浸润分析,对关键基因尿皮质素(UCN)进行了进一步研究。我们的结果显示,UCN 高表达与关键免疫细胞(包括 B 细胞、CD4+ 细胞毒性 T 细胞、CD8+ T 细胞和 NKT 细胞)丰度降低之间存在显著相关性。功能实验表明,在 CRC 细胞系中干扰 UCN 基因可显著降低癌细胞增殖,凸显了 UCN 在肠道免疫调节中的作用。所开发的以 UCN 为核心的预后模型提高了预后预测的准确性,并为 CRC 的诊断和治疗干预提供了重要见解。
Colorectal cancer (CRC), a prevalent malignancy, ranks third in global incidence and second in mortality rates. Despite advances in screening methods such as colonoscopy, the accurate diagnosis of CRC remains challenging due to the absence of reliable biomarkers.
This study aimed to develop a robust prognostic model for precise CRC outcome prediction. Employing weighted co-expression network analysis (WGCNA) and Cox regression analysis on data from The Cancer Genome Atlas (TCGA), we identified a panel of 12 genes strongly associated with patient survival. This gene panel facilitated accurate CRC outcome predictions, which is also validated via the external validation cohort GSE17536.
We conducted further investigations into the key gene, urocortin ( UCN ), using single-cell transcriptomic data and immune infiltration analysis in CRC patients.
Our results revealed a significant correlation between high UCN expression and the reduced prevalence of key immune cells, including B cells, CD4+ cytotoxic T cells, CD8+ T cells, and NKT cells. Functional experiments showed that UCN gene interference in the CRC cell lines significantly decreased cancer cell proliferation, underscoring UCN 's role in intestinal immunity modulation. The UCN -centric prognostic model developed enhances prognosis prediction accuracy and offers critical insights for CRC diagnosis and therapeutic interventions.
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