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:Development and Validation of an Immune Prognostic Index Related to Infiltration of CD4+ and CD8+ T Cells in Colorectal Cancer.
Development and Validation of an Immune Prognostic Index Related to Infiltration of CD4+ and CD8+ T Cells in Colorectal Cancer.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
结直肠癌(CRC)是全球范围内高度流行的癌症,但具有相似临床或历史分期的患者其治疗结局可能差异显著。本研究旨在探讨CRC患者恶性进展相关的免疫细胞丰度差异。
我们利用来自The Cancer Genome Atlas的CRC患者数据作为训练集。为评估免疫细胞浸润水平,计算了免疫细胞风险评分(ICRS)。
此外,我们进行了网络分析以识别有效T细胞相关基因(ETRGs),并随后构建了有效T细胞预后指数(ETPI)。通过使用四个Gene Expression Omnibus数据集进行外部验证,评估了ETPI的性能。
此外,还进行了列线图分析和药物敏感性分析,以探索ETRGs的临床效用。我们还检测了ETRGs在临床样本中的表达。基于ICRS,我们确定活化的CD4+和CD8+ T细胞是预后方面的保护因素。识别出六个ETRGs用于开发ETPI,其表现出显著的预后性能。在免疫治疗的外部验证中,低ETPI组显示出显著较低的复发率。为优化治疗策略,我们开发了列线图。
值得注意的是,不同ETPI值的患者对肿瘤通路抑制剂表现出不同的反应。最后,我们观察到某些ETRGs在正常组织中的蛋白表达高于肿瘤组织。
我们的研究结果表明,ETPI可能有助于基于肿瘤微环境和关键基因组景观相互作用精确选择患者,从而优化药物获益并在未来为临床策略提供信息。
Colorectal cancer (CRC) is a highly prevalent cancer worldwide, but treatment outcomes can vary significantly among patients with similar clinical or historical stages.
This study aimed to investigate the differences in immune cell abundance associated with malignant progression in CRC patients.
We utilized data from patients with CRC obtained from The Cancer Genome Atlas as our training set. To assess immune cell infiltration levels, an immune cell risk score (ICRS) was calculated.
Furthermore, we performed network analysis to identify effective T cell-related genes (ETRGs) and subsequently constructed an effective T cell prognostic index (ETPI). The performance of the ETPI was evaluated through external validation using four Gene Expression Omnibus datasets.
Additionally, a nomogram analysis and drug sensitivity analysis were conducted to explore the clinical utility of the ETRGs.
We also examined the expression of ETRGs in clinical samples. Based on the ICRS, we identified activated CD4+ and CD8+ T cells as protective factors in terms of prognosis. Six ETRGs were identified to develop the ETPI, which exhibited remarkable prognostic performance. In the external validation of immunotherapy, the low ETPI group demonstrated a significantly lower recurrence rate. To optimize therapeutic strategies, we developed a nomogram.
Notably, patients with different ETPI values exhibited varying responses to tumor pathway inhibitors.
Finally, we observed higher protein expression of certain ETRGs in normal tissues compared to tumors. Our findings suggest that the ETPI may contribute to the precise selection of patients based on tumor microenvironment and key genomic landscape interactions, thereby optimizing drug benefits and informing clinical strategies in future.
MEMBER ACCOUNT
登录成功会直接打开下一页。