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MUC1通过损害抗肿瘤免疫促进肝癌的肺转移。

MUC1 promotes lung metastases of liver cancer by impairing anti-tumor immunity.

作者信息

Yin Yanze, Yang Changjie, Xu Jiafeng, Luo Yi, Xia Qiang, He Kang

机构信息

Department of Liver Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai, China.

出版信息

Discov Oncol. 2023 Feb 4;14(1):18. doi: 10.1007/s12672-023-00627-0.

DOI:10.1007/s12672-023-00627-0
PMID:36738352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9899301/
Abstract

PURPOSE

MUC1 is a membrane bound protein that can regulate tumor progression but its role in tumor metastasis and the metastatic microenvironment remains unclear.

METHODS

We performed differential gene analysis for primary liver cancer (n = 31) and lung metastases (n = 31) using the Gene Expression Omnibus (GEO) dataset (GSE141016) and obtained RNA sequencing data from 374 liver cancer and 50 normal tissues from The Cancer Genome Atlas (TCGA). We analyzed the prognostic value of MUC1 and the relationship between MUC1 and the TME using online databases and a clinical cohort. Immunohistochemistry detected MUC1 in normal liver, liver cancer, and lung metastases. Multiplex immunohistochemistry staining detected immune cells in the metastatic microenvironment.

RESULTS

High MUC1 expression levels in hepatocellular carcinoma are associated with worse clinical prognosis and higher rates of lung metastasis. In addition, we observed a correlation between MUC1 and multiple immune cells in the metastatic microenvironment. In paired primary liver cancer and lung metastatic tumor tissues from the same patient, we observed higher MUC1 protein levels in lung metastases than in primary liver cancer. Furthermore, MUC1 was negatively correlated with CD8+T and Treg cells in the metastatic tumor microenvironment and positively correlated with DC. In addition, we found that MUC1 was associated with CD8+T cell activation and function using flow cytometry in another cohort of patients with liver cancer.

CONCLUSION

These data confirm the potential of MUC1 as a prognostic marker and therapeutic target.

摘要

目的

MUC1是一种膜结合蛋白，可调节肿瘤进展，但其在肿瘤转移和转移微环境中的作用仍不清楚。

方法

我们使用基因表达综合数据库（GEO）数据集（GSE141016）对原发性肝癌（n = 31）和肺转移癌（n = 31）进行差异基因分析，并从癌症基因组图谱（TCGA）获得374例肝癌和50例正常组织的RNA测序数据。我们使用在线数据库和临床队列分析了MUC1的预后价值以及MUC1与肿瘤微环境（TME）之间的关系。免疫组织化学检测正常肝脏、肝癌和肺转移癌中的MUC1。多重免疫组织化学染色检测转移微环境中的免疫细胞。

结果

肝细胞癌中高MUC1表达水平与较差的临床预后和较高的肺转移率相关。此外，我们观察到MUC1与转移微环境中的多种免疫细胞之间存在相关性。在来自同一患者的配对原发性肝癌和肺转移瘤组织中，我们观察到肺转移癌中的MUC1蛋白水平高于原发性肝癌。此外，MUC1在转移瘤微环境中与CD8 + T细胞和调节性T细胞呈负相关，与树突状细胞呈正相关。此外，我们在另一组肝癌患者中使用流式细胞术发现MUC1与CD8 + T细胞的激活和功能相关。

结论

这些数据证实了MUC1作为预后标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/0024ee3e76f5/12672_2023_627_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/b2d03482a837/12672_2023_627_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/4f5b1764edcc/12672_2023_627_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/12e3c852940e/12672_2023_627_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/e28fffb30fd0/12672_2023_627_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/dbb55bbbc1a5/12672_2023_627_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/0024ee3e76f5/12672_2023_627_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/b2d03482a837/12672_2023_627_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/4f5b1764edcc/12672_2023_627_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/12e3c852940e/12672_2023_627_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/e28fffb30fd0/12672_2023_627_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/dbb55bbbc1a5/12672_2023_627_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/9899301/0024ee3e76f5/12672_2023_627_Fig6_HTML.jpg

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Overexpression of MUC1 Induces Non-Canonical TGF-β Signaling in Pancreatic Ductal Adenocarcinoma.MUC1过表达在胰腺导管腺癌中诱导非经典TGF-β信号传导。
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