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:Breast cancer combined prognostic model based on lactate metabolism genes.
Breast cancer combined prognostic model based on lactate metabolism genes.
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本研究旨在探讨乳酸代谢基因、乳酸代谢相关基因(LMRG)及免疫浸润细胞对乳腺癌预后的影响。研究通过单细胞测序鉴定LMRG,并采用CIBERSORT评估免疫细胞浸润。通过Cox回归和最小绝对收缩与选择算子(LASSO)方法筛选预后基因,并采用差异分析确定乳酸代谢相关的免疫浸润细胞。GSE20685数据集用于外部验证。通过生存、免疫微环境和药物敏感性分析评估模型的预后价值。NDUFAF6与乳腺癌预后关系最密切;研究共获得450个LMRG。SUSD3、IL18、MAL2和CDKN1C构成Model2。NK细胞活化与乳酸代谢关联最强。联合预后模型优于单一模型,在三个队列中的曲线下面积均为0.7–0.8。乳酸代谢相关联合模型有助于评估乳腺癌预后,并为治疗尤其是免疫治疗提供新线索。
To investigate the impact of lactate metabolism genes, lactate metabolism-related genes (LMRG), and immune infiltrating cells on the prognosis of breast cancer. LMRG was identified via single-cell sequencing. Immune cell infiltration was obtained by the CIBERSORT method. The prognostic genes were chosen by cox regression and the least absolute selection operator approach.
lactate metabolism-associated immune-infiltrating cells was determined by difference analysis. The GSE20685 dataset was used as an external validation cohort. The model's prognostic usefulness was evaluated utilizing survival, immunological microenvironment, and drug sensitivity assessments. NDUFAF6 was most associated with breast cancer prognosis.
We obtained a total of 450 LMRG. SUSD3, IL18, MAL2, and CDKN1C comprised the Model2. NK cell activation was most relevant to lactate metabolism. The combined prognostic model outperformed the individual model, with the area under the curve ranging from 0. 7 to 0. 8 in all three cohorts. The lactate metabolism-related combination model assisted in evaluating breast cancer prognosis, providing new insights for treatment, particularly immunotherapy.
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