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
一项整合分析识别 RAB40C 为肺鳞状细胞癌的致癌免疫蛋白和预后标志物
英文原题：An Integrative Analysis Identifying RAB40C as an Oncogenic Immune Protein and Prognostic Marker of Lung Squamous Cell Carcinoma.
查看英文原题
An Integrative Analysis Identifying RAB40C as an Oncogenic Immune Protein and Prognostic Marker of Lung Squamous Cell Carcinoma.
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研究概要
RAB40C 可作为 LUSC 治疗的有效预后生物标志物和潜在的免疫治疗靶点。
研究思路结论见上方概要
背景
RAB40C是Ras癌基因家族的一员，是一种具有GTPase和GTP结合活性的蛋白，也被预测在免疫调节中具有重要作用。然而，RAB40C与肺鳞状细胞癌（LUSC）之间的联系尚未阐明。探索RAB40C与LUSC之间的关系有助于扩展LUSC的免疫治疗靶点库，并为LUSC患者提供更有效的治疗选择，这代表了我们的研究目的。
方法
我们基于TCGA数据库分析了RAB40C在不同肿瘤类型和分期中的表达。随后，我们通过免疫组化分析探讨了RAB40C在LUSC与癌旁组织中的表达差异。通过Cox回归和Kaplan-Meier分析评估了RAB40C的预后价值。使用TIMER2.0和CIBERSORT分析工具获得了基于基因集富集分析的RAB40C影响通路以及RAB40C表达与免疫浸润之间的相关性。通过Spearman相关分析评估了肿瘤突变负荷和微卫星不稳定性（MSI）。最后，通过将免疫细胞浸润与免疫调节因子表达相关联、结合其他因素评估风险评分以及分析预后列线图，探讨了RAB40C与LUSC的密切关联。
结果
RAB40C在LUSC中表达显著升高。RAB40C表达与免疫因子、免疫相关通路及MSI显著相关。此外，RAB40C与LUSC相关免疫浸润细胞、CD4记忆活化细胞、γδ T细胞、M1样巨噬细胞及免疫调节因子CD28显著负相关，而与Tregs和NK 细胞的活化正相关。进一步，由RAB40C及其相关免疫基因构建的风险模型显示，RAB40C可能是LUSC的独立预后因素。
展开英文摘要原文
BACKGROUND
RAB40C, a member of the Ras oncogene family, is a protein with GTPase and GTP-binding activity and is also predicted to be important in immunomodulation. However, the link between RAB40C and lung squamous cell carcinoma (LUSC) has not yet been elucidated. Exploring the relationship between RAB40C and LUSC could help expand the repertoire of immunotherapeutic targets for LUSC and provide more effective therapeutic options for LUSC patients, which behalf of our aim for our study.
METHODS
We analyzed the RAB40C expression in different tumor types and stages based on the TCGA database. Subsequently, we explored the differences in RAB40C expression in LUSC versus paracancerous tissues through immunohistochemical analysis. The prognostic value of RAB40C was assessed by Cox regression and Kaplan-Meier analysis. Gene set enrichment analysis-based RAB40C impact pathways and the correlation between RAB40C expression and immune infiltration were obtained using the TIMER2.0 and the CIBERSORT analytical tools. Tumor mutational load and microsatellite instability (MSI) were assessed by the Spearman correlation analysis. Finally, the close association of RAB40C with LUSC was explored by correlating immune cell infiltration with immunomodulator expression, assessing risk scores in combination with other factors, and analyzing prognostic nomogram.
RESULTS
The expression of RAB40C was significantly elevated in LUSC. RAB40C expression was significantly associated with immune factors, immune-related pathways, and MSI. Moreover, RAB40C significantly negatively correlated with LUSC-associated immune infiltrating cells, CD4 memory-activated cells, γδ T cells, M1-like macrophages, and the immune regulator CD28, while it positively associated with the activation of Tregs and natural killer cells. Further, a risk model constructed from RAB40C and its associated immune genes showed that RAB40C might be an independent prognostic factor for LUSC.
CONCLUSION
RAB40C can be used as an effective prognostic biomarker and a potential immunotherapeutic target for the treatment of LUSC.
论文信息
- 作者
- Wu H、Dong X、Liao L、Huang L
- 第一作者单位
- Department of Pneumology, Yiwu Central Hospital, Yiwu, Zhejiang, People's Republic of China.China
- 通讯作者单位
- Department of Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.China
- 期刊
- Pharmacogenomics and personalized medicine2022
- 原文标识
- PubMed 35645578 · DOI 10.2147/PGPM.S357166
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