Background
Patients diagnosed with hepatocellular carcinoma (HCC) generally have an unfavorable outlook, with lung metastasis being a prevalent factor contributing to mortality. The metastatic microenvironment is critical to the tumor metastatic process. The exact impact of Triggering Receptor Expressed on Myeloid Cells 1 (TREM1) on tumor metastasis and the microenvironment of metastasis is still not known. By analyzing online databases and a clinical cohort, we evaluated the predictive significance of TREM1 and its correlation with the tumor microenvironment (TME).
Conclusions
Increased expression of TREM1 in HCC is linked to a poorer clinical outlook and elevated incidence of lung metastasis, suggesting its potential as a prognostic biomarker for patients with liver cancer lung metastasis.
Methods
Using the Gene Expression Omnibus (GEO) dataset (GSE141016), genes differentially expressed in liver cancer and lung metastases were analyzed. Data from liver hepatocellular carcinoma (LIHC) of The Cancer Genome Atlas (TCGA) were acquired through RNA sequencing. The abundance of tumor-infiltrating immune cells was estimated using Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE). The single sample gene set enrichment analysis (ssGSEA) algorithm was utilized to determine the association between TREM1 and immune cells. The level of TREM1 and immune cells were determined in formalin-fixed paraffin-embedding (FFPE) specimens.
Results
Increased expression of TREM1 in HCC was linked to a poorer clinical prognosis and elevated incidence of lung metastasis. Furthermore, TREM1 was found to be associated with multiple immune cells in the TME. We noticed that lung metastases in the same patient had higher levels of TREM1 protein compared to primary liver cancer. Additionally, lung metastases exhibited increased neutrophil numbers and neutrophil extracellular traps (NETs) formation compared to primary liver cancer. Moreover, there was a positive correlation between TREM1 and both neutrophils and NETs. Conclusions: Increased expression of TREM1 in HCC is linked to a poorer clinical outlook and elevated incidence of lung metastasis, suggesting its potential as a prognostic biomarker for patients with liver cancer lung metastasis.