Combined single-cell RNA-seq and bulk RNA-seq to analyze the expression and role of TREM2 in bladder cancer

Currently, reprogramming macrophages has emerged as one of the most promising therapeutic strategies in cancer treatment. Many studies have found that myeloid trigger receptor-2 (TREM2) is mainly expressed on tumor-associated macrophages (TAMs), and targeting TREM2 promotes reprogramming of TAMs and enhances the immunotherapeutic effect of tumors. Nevertheless, the expression and role of TREM2 in different tumor tissues are still controversial. For example, some studies have found that TREM2 can also be expressed on tumor cells and exert pro-tumor functions. It has also been found that TREM2 expression can inhibit tumorigenesis and progression. In fact, there are still no relevant studies on the expression and role of TREM2 in bladder cancer (BLCA). Therefore, the present study combined single-cell RNA-seq and bulk RNA-seq to analyze the expression, role, and molecular mechanism of TREM2 in BLCA. We found that TREM2 was predominantly expressed on TAMs in BLCA, followed by tumor epithelial cells. This finding could be useful for further exploration of the role and mechanism of TREM2. Moreover, TREM2 expression correlates with clinical progression and immunotherapy efficacy, and is an important predictor of prognosis for BLCA patients. Not only that, we also found that TREM2 may exert its effects by promoting epithelial mesenchymal transition (EMT) and T-cell exhaustion. TREM2+ TAMs may play an important pro-tumor role through PTN, ANGPTL, and VISFATIN pathways. In conclusion, our study found that TREM2 is not only a predictor of BLCA prognosis, but also a potential therapeutic target for BLCA.