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:Comprehensive analysis of COLGALT1 in tumor microenvironment regulation and prognosis of clear cell renal cell carcinoma.
Comprehensive analysis of COLGALT1 in tumor microenvironment regulation and prognosis of clear cell renal cell carcinoma.
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胶原半乳糖基转移酶1(COLGALT1)是参与胶原翻译后修饰的关键酶,已被认为与多种癌症类型的细胞外基质重塑有关,但其在透明细胞肾细胞癌(ccRCC)中的预后意义及其与肿瘤免疫微环境的关系仍不清楚。
在本研究中,我们分析了来自公共数据库的多组学数据集,以评估COLGALT1在ccRCC中的表达模式、临床相关性和预后价值。采用实时定量PCR验证其在肾癌细胞系和正常肾小管上皮细胞中的表达。使用多种计算算法表征免疫浸润特征,并构建竞争性内源RNA网络以探索调控机制。
我们的结果表明,COLGALT1在ccRCC中mRNA和蛋白水平均显著上调,并与单核细胞、T辅助2细胞、巨噬细胞、调节性T细胞和NK 细胞的浸润呈正相关。
值得注意的是,COLGALT1表达与M2巨噬细胞标志物密切相关,提示其在促进免疫抑制性肿瘤微环境中发挥作用。这些发现表明COLGALT1是ccRCC中一种新的预后生物标志物和潜在治疗靶点,突出了其在细胞外基质重塑和免疫调节中的贡献。
Collagen galactosyltransferase 1 (COLGALT1), a key enzyme involved in collagen post-translational modification, has been implicated in extracellular matrix remodeling across multiple cancer types, yet its prognostic significance and relationship with the tumor immune microenvironment in clear cell renal cell carcinoma (ccRCC) remain unclear.
In this study, we analyzed multi-omics datasets from public repositories to assess COLGALT1 expression patterns, clinical relevance, and prognostic value in ccRCC. Quantitative real-time PCR was performed to validate its expression in renal cancer cell lines and normal renal tubular epithelial cells. Immune infiltration profiles were characterized using multiple computational algorithms, and a competing endogenous RNA network was constructed to explore regulatory mechanisms.
Our results demonstrated that COLGALT1 expression was significantly upregulated in ccRCC at both mRNA and protein levels and was positively associated with the infiltration of monocytes, T helper 2 cells, macrophages, regulatory T cells, and natural killer cells.
Notably, COLGALT1 expression correlated strongly with markers of M2 macrophages, suggesting a role in promoting an immunosuppressive tumor microenvironment.
These findings identify COLGALT1 as a novel prognostic biomarker and potential therapeutic target in ccRCC, highlighting its contribution to extracellular matrix remodeling and immune regulation.
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