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

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Abstract

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.

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Data availability

All data are from public databases. The TCGA-BLCA dataset can be downloaded from the TCGA Data Portal (https://portal.gdc.cancer.gov/). The IMvigor210 cohort dataset can be downloaded from the website: http://research-pub.gene.com/IMvigor210CoreBiologies/. Single-cell datasets are available for download from the GEO public database (https://www.ncbi.nlm.nih.gov/geo/).

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Funding

This work was supported by the key research and development (R&D) projects of Gansu Province (Grant No. 17YF1FA126); Lanzhou Science and Technology Bureau Medical and Health Project (Grant No. 2021–90); and Special fund project for doctoral training program of Lanzhou University Second Hospital (Grant No.YJS-BD-25).

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Authors and Affiliations

  1. Department of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Institute of Urology, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China

    Xingxing Zhang, Yuelin Du, Wei Xiong & Panfeng Shang

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  1. Xingxing Zhang
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  2. Yuelin Du
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  3. Wei Xiong
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  4. Panfeng Shang
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Contributions

PS: contributed to the study conception and design. Material preparation, data collection, and analysis were performed by XZ, YD, and WX. The first draft of the manuscript was written by XZ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Panfeng Shang.

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Zhang, X., Du, Y., Xiong, W. et al. Combined single-cell RNA-seq and bulk RNA-seq to analyze the expression and role of TREM2 in bladder cancer. Med Oncol 40, 23 (2023). https://doi.org/10.1007/s12032-022-01885-8

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