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
基于生物信息学分析探索转移性结直肠癌的有效生物标志物和浸润免疫细胞
英文原题：Exploration of effective biomarkers and infiltrating immune cells in metastatic colorectal cancer based on bioinformatics analysis.
查看英文原题
Exploration of effective biomarkers and infiltrating immune cells in metastatic colorectal cancer based on bioinformatics analysis.
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中文摘要
结直肠癌（CRC）是全球第三大常见恶性肿瘤，也是全球癌症相关死亡的第二大原因。转移性结直肠癌（mCRC）在临床上被归类为晚期恶性肿瘤，其特征是治疗耐药和生存结局显著降低。mCRC 的 5 年生存率显著低于早期 CRC。
我们实施了一个多维计算框架来剖析 CRC 转录组学。从 TCGA 和 GEO 数据库中系统获取了基因表达谱。随后使用 ssGSEA 算法、xCell 算法、edgeR、limma、DAVID 富集分析、CytoHubba、ROC 逻辑回归和相关分析对一系列数据进行了分析。免疫细胞浸润分析显示，7 种肿瘤浸润免疫细胞亚型在转移性与非转移性结直肠癌队列之间表现出显著的丰度差异。
进一步的整合分析在转移病灶中鉴定了 28 个免疫相关转移性结直肠癌差异表达基因（ICDEGs）。通过综合分析，成功鉴定了 9 个关键枢纽基因（AGTR1、CD86、CMKLR1、FGF1、FYN、IL10RA、INHBA、TNFSF13B 和 VEGFC）。
值得注意的是，AGTR1、CD86、CMKLR1 和 TNFSF13B 基因在 mCRC 中鲜有报道。此外，我们的相关性研究揭示了上皮细胞与三个特定基因 TNFSF13B、CD86 和 IL10RA 之间存在显著的负相关关系。所鉴定的 9 个枢纽基因显示出作为 mCRC 可靠诊断生物标志物的巨大潜力。
此外，这些分子标志物可能通过与肿瘤浸润免疫细胞的动态相互作用参与疾病发病机制，提示其在肿瘤微环境中发挥关键作用。
展开英文摘要原文
Colorectal cancer (CRC) ranks as the third most prevalent malignancy globally and represents the second leading cause of cancer-related mortality worldwide. Metastatic colorectal cancer (mCRC) is clinically classified as an advanced-stage malignancy, characterized by therapeutic resistance and substantially diminished survival outcomes. The 5-year survival rate for mCRC is significantly lower than that for early-stage CRC. A multi-dimensional computational framework was implemented to dissect CRC transcriptomics.
Gene expression profiles were systematically acquired from TCGA and GEO repositories. A series of data were then analyzed using ssGSEA algorithm, xCell algorithm, edgeR, limma, DAVID enrichment analysis, CytoHubba, ROC logistic regression and correlation analysis. Immune cell infiltration analysis revealed 7 tumor-infiltrating immune cell subtypes exhibiting significant abundance disparities between metastatic and non-metastatic colorectal cancer cohorts.
Further integrative analysis identified 28 immune-related metastatic colorectal cancer differentially expressed genes (ICDEGs) in metastatic lesions. Through comprehensive analysis, 9 pivotal hub genes (AGTR1, CD86, CMKLR1, FGF1, FYN, IL10RA, INHBA, TNFSF13B, and VEGFC) were successfully identified.
Notably, AGTR1, CD86, CMKLR1 and TNFSF13B genes have been rarely reported in mCRC.
Furthermore, our correlation studies revealed significant inverse relationships between epithelial cells and three specific genes: TNFSF13B, CD86, and IL10RA. The identified 9 hub genes demonstrate significant potential as reliable diagnostic biomarkers for mCRC.
Moreover, these molecular markers may contribute to disease pathogenesis through their dynamic interactions with tumor-infiltrating immune cells, suggesting a crucial role in the tumor microenvironment.
论文信息
- 作者
- Huang J、Guo Y、Lv X、Long Y、Wang X、Jin D、Liu H
- 第一作者单位
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China.China
- 通讯作者单位
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China. gzuhmliu@126.com.China
- 期刊
- Scientific reports2025 Sep 26
- 原文标识
- PubMed 41006647 · DOI 10.1038/s41598-025-18589-4
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