High Expression of Triggering Receptor Expressed on Myeloid Cells 1 Predicts Poor Prognosis in Glioblastoma

Abstract

Background

Glioblastoma (GBM) is a highly malignant tumor with poor prognosis, and new treatment strategies are urgently needed. Currently, the role of triggering receptor expressed on myeloid cells 1 (TREM-1) in tumors has been studied, but the role of TREM-1 in GBM remains unclear.

Methods

Immunohistochemical staining for TREM-1 was performed in 91 patients diagnosed with GBM. Clinicopathological characteristics and survival times were recorded. TREM-1 expression and its effect on prognosis were analyzed using online Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA) databases. The expression profile of TCGA-GBM cohort was used to perform functional enrichment analysis. The CIBERSORT method and Tumor Immune Estimation Resource (TIMER) database were used to estimate the tumor-infiltrating immune cells (TIICs). The ESTIMATE algorithm was used to estimate the immune-stromal scores. Finally, the relationships of TREM-1 with TIICs, immune-stromal score, and immune checkpoint genes (ICGs) were analyzed.

Results

The expression of TREM-1 was upregulated in GBM, and high TREM-1 expression predicted a poor prognosis. TREM-1, surgical resection, postoperative radiotherapy, and temozolomide (TMZ) chemotherapy were associated with the survival time of patients with GBM, but only surgical resection and TREM-1 expression were independent prognostic factors. GBM with high TREM-1 expression exhibited increased neutrophil and macrophage infiltration. TREM-1 was positively associated with the immune-stromal score and multiple ICGs, and most of which were involved in immunosuppressive responses.

Conclusion

The present study revealed that high expression of TREM-1 in GBM is an independent poor prognosis factor and that TREM-1 is associated with the immunosuppressive microenvironment. Thus, blocking TREM-1 may be a strategy for enhancing the GBM immune response.

Keywords:

• TREM-1
• tumor-infiltrating immune cells
• immune checkpoint genes
• prognosis
• glioblastoma

Data Sharing Statement

All the datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

The present study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Henan Provincial People’s Hospital. Written informed consent was obtained from all patients or the patients’ parents.

Consent for Publication

All authors agreed to publish the paper in any form.

Acknowledgments

The results shown here are in part based upon data generated by the following publicly available databases: TCGA (https://www.cancer.gov/tcga), CGGA (https://www.cgga.org.cn/), GEPIA (https://gepia.cancer-pku.cn/), and TIMER (https://gepia.cancer-pku.cn/). We express our sincere thanks to the contributors of these databases. A preprint of the paper has previously been published by Ma K et al in 2022 (https://www.researchsquare.com/article/rs-1655537/v1).

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This research was funded by the Natural Science Foundation of Henan Province (Grant No. 212300410251) and the Henan Medical Science and Technology Foundation (Grant No. 2018020022).