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:Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.
Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.
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我们的研究表明,肿瘤组织的微生物组分析可以预测 TNBC 患者的化疗反应。此外,免疫肿瘤微环境可能受到肿瘤微生物组的影响,从而影响相应的生存和治疗反应。
三阴性乳腺癌(TNBC)是一种预后不良且具有独特肿瘤微环境的乳腺癌亚型。对肿瘤微生物组的分析表明,肿瘤微环境与治疗反应之间存在关系。因此,我们试图揭示肿瘤微生物组在接受新辅助化疗的TNBC患者中的作用。
我们从Gene Expression Omnibus收集了TNBC患者的RNA测序样本,并提取了微生物组计数数据。采用线性判别分析效应量估计差异丰度和相对丰度。我们使用CIBERSORTx计算了免疫细胞比例,并利用癌症基因组图谱患者数据进行了生存分析。分析了微生物组与免疫细胞组成之间的相关性,并构建了一个预测模型以评估药物反应。
在病理完全缓解组(pCR)中,β多样性差异很大;因此,观察到20个属和24个种表现出显著的差异和相对丰度。Pandoraea pulmonicola和Brucella melitensis被发现是决定药物反应的重要特征。在相关性分析中,Geosporobacter ferrireducens、Streptococcus sanguinis和静息NK 细胞是pCR中相关性最强的因素,而Nitrosospira briensis、Plantactinospora sp. BC1和调节性T细胞是残留病灶组的关键特征。
Triple-negative breast cancer (TNBC) is a breast cancer subtype that has poor prognosis and exhibits a unique tumor microenvironment. Analysis of the tumor microbiome has indicated a relationship between the tumor microenvironment and treatment response. Therefore, we attempted to reveal the role of the tumor microbiome in patients with TNBC receiving neoadjuvant chemotherapy.
We collected TNBC patient RNA-sequencing samples from the Gene Expression Omnibus and extracted microbiome count data. Differential and relative abundance were estimated with linear discriminant analysis effect size. We calculated the immune cell fraction with CIBERSORTx and conducted survival analysis using the Cancer Genome Atlas patient data. Correlations between the microbiome and immune cell compositions were analyzed and a prediction model was constructed to estimate drug response.
Among the pathological complete response group (pCR), the beta diversity varied considerably; consequently, 20 genera and 24 species were observed to express a significant differential and relative abundance. Pandoraea pulmonicola and Brucella melitensis were found to be important features in determining drug response. In correlation analysis, Geosporobacter ferrireducens, Streptococcus sanguinis, and resting natural killer cells were the most correlated factors in the pCR, whereas Nitrosospira briensis, Plantactinospora sp. BC1, and regulatory T cells were key features in the residual disease group.
Our study demonstrated that the microbiome analysis of tumor tissue can predict chemotherapy response of patients with TNBC. Further, the immunological tumor microenvironment may be impacted by the tumor microbiome, thereby affecting the corresponding survival and treatment response.
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