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

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.

Fibrotic Phenotype in CRISPR knockout p53 of Hepatic Organoids within a Pro-Carcinogenic Microenvironment

“…Notably, a cluster of genes associated with early cancer initiation and progression, including MYC, CD44, ALDH4A1, MUC1, GPC3 and GPC4 exhibited signi cantly elevated expression levels in TP53KO-eHEPOs. Due to the wide acceptance of these markers in the initiation of liver cancer and their high expression in various other cancers, they hold potential as therapeutic targets [45][46][47][48]. The implications of these ndings are further substantiated by previous research.…”

“…To explore the role of TP53KO-eHEPOs in liver cancer initiation and progression, we examined several well-conserved markers in our transcriptome dataset. We observed an increased signal in TP53KO-eHEPOs for tumorigenesis markers associated with cancer initiation and/or progression, including CD44, MYC, MUC1, and CD36 [45][46][47][48] (Fig. 3E).…”

Accurate and noninvasive diagnosis of epithelial cancers through AND gate photoluminescence on tumor-derived small extracellular vesicles

“…), which was consistent with other research results. 39,40 However, when the lanthanide luminescence probe system was applied to detect plasma samples that do not exhibit high-levels of co-expression of EpCAM and MUC1 antigens on sEVs only the fluorescence signals at the same level as those found in the healthy control group can be detected. These results indicated that our AND gate photoluminescence strategy can be applied to detect plasma samples with expression of both sEVs' EpCAM and MUC1, to reveal the existence of the epithelial cancers accurately.…”