TREM2 Is a Prognostic Biomarker and Correlated with an Immunosuppressive Microenvironment in Thyroid Cancer

To identify the differentially expressed genes (DEGs) related to the immune microenvironment and elucidate the biological functions of key genes in papillary thyroid cancer (PTC) by analyzing the immune microenvironment.

The relative quantities of immune and matrix components in 507 patients with PTC were calculated from the TCGA database. Analysis of differentially expressed genes in tumor samples throughout the genome, intersection of DEGs obtained from PTC patients, and genome-wide tumor samples and survival analysis were performed. Survival analysis was used for identification of prognostic factor. Immunohistochemical analysis of the TREM2 expression in PTC tissues, flow cytometry, and transwell assays were used to detect the effect of TREM2 on PTC cell proliferation, migration, and invasion.

There were a total of 1242 upregulated genes with high intersection in the immune score and 124 downregulated genes with low intersection in the stromal score. A total of 1,366 genes in these DEGs may be determinants in the immune microenvironment. GO enrichment and KEGG enrichment analysis revealed that the overall function of DEGs appeared to map onto immune-related activities. Gene intersection and survival analysis showed that there were 435 DEG crosses in PTC patients and genome-wide tumor samples, only CXCL10, CD40LG, KRT14, TRAT1, and TREM2 were associated with patient prognosis, and TCGA showed that only the TREM2 expression was upregulated in PTC. TREM2 knockdown inhibited the cell cycle and cell proliferation, migration, and invasion by PTC cells. TREM2 was associated with the immunosuppressive microenvironment by via NF-κB pathway in PTC.

TREM2 possibly was a potential indicator of altered TME status in PTC, and that TREM2 promoted PTC cell proliferation and cell cycle, migration, and invasion by NF-κB pathway.