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 CXCL14 uncovers its role during liver metastasis in colon cancer.
Comprehensive analysis of CXCL14 uncovers its role during liver metastasis in colon cancer.
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我们的结果可以提高对结肠癌肝转移过程的理解。此外,CXCL14 被确定为结肠癌的潜在治疗靶点。
结肠癌患者最常见的死亡原因是肝转移。
本研究纳入的所有数据均下载自两个公共数据库,即癌症基因组图谱计划(The Cancer Genome Atlas Program)的 TCGA-COAD 项目和基因表达综合数据库(Gene Expression Omnibus)的 GSE41258 项目。所有分析均在 R 软件中完成。
在我们的研究中,我们系统地探索了参与结肠癌肝转移过程的分子。通过GO和KEGG分析鉴定了这些分子的生物学作用。此外,我们确定分子SERPINA3、SERPINA1、MMP3、ALDH1A3、PBK和CXCL14是患者生存的独立因素。由于P值最显著,CXCL14被选为进一步分析的对象。单细胞分析显示CXCL14主要在成纤维细胞中表达。同时,研究了成纤维细胞在结肠癌微环境中的生物学作用。进一步,还探索了CXCL14在结肠癌中的临床作用。结果显示,CXCL14是结肠癌的保护因素,独立于年龄、性别、临床分期和TNM分类等其他临床参数。然后,生物学富集分析表明,CXCL14主要参与WNT/β/catenin通路、胰腺β细胞、过氧化物酶体和胆汁酸代谢的激活。免疫浸润分析显示,对于CXCL14水平高的患者,血浆B细胞、CD8+ T细胞、中性粒细胞和NK细胞可能浸润更多,而B细胞、单核细胞和巨噬细胞则相反。此外,我们发现CXCL14表达低的患者可能对etoposide、rapamycin和sunitinib更敏感。
The most common cause of death for colon cancer patients is liver metastasis.
All the data enrolled in this study were downloaded from two public databases, The Cancer Genome Atlas Program, the TCGA-COAD project and Gene Expression Omnibus, GSE41258 project. All the analysis was performed in R software.
In our study, we systematically explored the molecules involved in the liver metastasis process of colon cancer. The biological role of these molecules was identified through the GO and KEGG analysis. Moreover, we identified that the molecules SERPINA3, SERPINA1, MMP3, ALDH1A3, PBK and CXCL14 were the independent factors for patients survival. The CXCL14 was selected for further analysis for its most significant P value. Single-cell analysis showed that the CXCL14 was mainly expressed in the fibroblasts. Meanwhile, the biological role of fibroblasts in the colon cancer microenvironment was investigated. Further, the clinical role of CXCL14 in colon cancer was also explored. The result showed that the CXCL14 is a protective factor against colon cancer independent of other clinical parameters like age, gender, clinical stage, and TNM classifications. Then, biological enrichment analysis indicated that the CXCL14 is predominantly involved in the activating of the WNT/β/catenin pathway, pancreas beta cells, peroxisome and bile acid metabolism. Immune infiltration analysis showed that for the patients with high CXCL14 levels, the plasma B cells, CD8 + T cells, neutrophil and NK cells might infiltrate more, in contrast to B cells, monocyte and macrophages. Furthermore, we found that the patients with low CXCL14 expression might be more sensitive to etoposide, rapamycin and sunitinib.
Our result could improve the understanding of the liver metastasis process in colon cancer. Also, CXCL14 was identified as an underlying therapeutic target for colon cancer.
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