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:Which dominates recurrence: tumor or microenvironment?
Which dominates recurrence: tumor or microenvironment?
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肺鳞状细胞癌(LUSC)因其高复发率而成为肿瘤学中的一大挑战,这凸显了识别复发驱动因素的必要性。基于张泽民团队在其研究中提供的数据,我们选取了119例肺鳞状细胞癌患者的生存元数据以及51种免疫细胞类型的比例数据。随后,我们结合机器学习方法分析了肺鳞状细胞癌(LUSC)复发中的肿瘤内在因素和肿瘤微环境(TME)。卡方检验识别出在复发患者中富集的免疫细胞亚群,如高MKI67 Tregs、低FGFBP2 NK细胞、低FOXP3 Tregs和低KLRB1 CD8+ T细胞。随机森林算法进一步确定病理缓解率(PRR)为主要预测因素,高MKI67 Tregs为关键的次要贡献因素。
单因素和多因素Cox回归分析以及Kaplan-Meier生存曲线证实,病理完全缓解(pCR)和低Treg_MKI67表达与更好的生存相关(分别为p = 0.0055和p = 0.011)。达到pCR且Treg_MKI67低表达的患者具有更优的无复发生存期(RFS;2年RFS:96.7% vs. 非pCR且高Treg_MKI67者为57.9%,p = 0.00066)。这些发现强调了PRR和TME标志物的预后价值。它们还凸显了利用单细胞RNA测序和机器学习来指导个性化治疗并通过靶向Treg活性降低复发风险的潜力,为将免疫标志物整合到临床实践中以改善LUSC预后奠定了基础。
Lung squamous cell carcinoma (LUSC) is a major challenge in oncology due to its high recurrence rate, highlighting the need to identify recurrence drivers. Based on the data provided by Zhang Zemin’s team in their research, we selected survival metadata from 119 patients with lung squamous cell carcinoma and data on the proportions of 51 immune cell types.
We then combined machine learning methods to analyze the intrinsic tumor factors and tumor microenvironment (TME) in the recurrence of lung squamous cell carcinoma (LUSC). Chi-square tests identified immune cell subsets enriched in recurrent patients, such as high-MKI67 Tregs, low-FGFBP2 NK cells, low-FOXP3 Tregs, and low-KLRB1 CD8 + T cells. A random forest algorithm further pinpointed pathological response rate (PRR) as the primary predictive factor, with high-MKI67 Tregs as a key secondary contributor.
Univariate and multivariate Cox regression analyses and Kaplan-Meier survival curves confirmed that pathological complete response (pCR) and low Treg_MKI67 expression were associated with better survival (p = 0. 0055 and p = 0. 011, respectively). Patients achieving pCR and with low Treg_MKI67 expression had superior recurrence-free survival (RFS; 2-year RFS: 96. 7% vs. 57. 9% for non-pCR and high Treg_MKI67, p = 0. 00066).
These findings underscore the prognostic value of PRR and TME markers. They also highlight the potential of using single-cell RNA sequencing and machine learning to guide personalized therapies and reduce recurrence risk by targeting Treg activity, laying the groundwork for integrating immune markers into clinical practice to improve LUSC prognosis.
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