TREM1 promotes cancer associated malignant phenotype through activated MAPK signaling pathway and predicts poor prognosis in gastric cancer.

Background: CD molecules plays a vital role in gastric cancer (GC). We used bioinformatics analysis methods to develop prognosis related CD molecules risk signature; On the other hand, we used the experiments to further explore the function and mechanism of differentially expressed prognostic CD molecules (TREM1) in GC.

Methods: Kaplan-Meier survival and univariate Cox regression analysis were used to evaluate the overall survival of CD molecule genes in gastric cancer. ROC curve and Kaplan-Meier curves were used to analyze the predictive value of CD molecule related genes risk signature by "survival and timeROC" R packages. GSEA, and Cibersortx software were used to analyze the functional enrichment. Finally, we verified the function and mechanism of TREM1 in GC by gene silencing and MAPK inhibitor (SB203580) in vitro and vivo.

Results: A total of 41 prognosis related risk factors in gastric cancer were identified based on CD molecules, including TREM1 and ect. The high-risk patients had higher risk score and shorter survival time. ROC curves revealed that this risk signature accurately predicted survival times of gastric cancer patients at the 1-, 2-, 3-, 4- and 5-year. The frequency of T cells follicular helper and NK cells activated were added in low-risk group. Next, differentially expressed prognostic CD molecules analysis revealed that TREM1 was identified as key genes in GC progression based on TCGA and GES158662 and GSE15459 datasets of GC. In vitro experiments, TREM1 silencing significantly inhibited GC cell proliferation and migration, induced cell apoptosis. GSEA revealed that TREM1 activated cancer related signaling pathway, including MAPK signaling pathway and ect. High expression of TREM1 was related Macrophages M2 and Mast cells resting in GC tissues. Moreover, knockdown of TREM1 inhibited tumor growth through downregulated MAPK signaling pathway in vivo.

Conclusion: These results identified that CD molecule related genes as a novel prognostic and diagnostic biomarker in gastric cancer. TREM1 acts as an oncogene role in GC by activated MAPK signaling pathway.