Overexpression of TREM1 is Associated with the Immune-Suppressive Microenvironment and Unfavorable Prognosis in Pan-Cancer

Xinwei Zhou; Ke Lin; Liangmin Fu; Fei Liu; Hansen Lin; Yuhang Chen; Bowen Zhuang; Hui Liang; Qiong Deng; Zhu Wang; Wei Chen; Junhang Luo; Jiazheng Cao; Pengju Li

doi:10.2147/JIR.S398284

Overexpression of TREM1 is Associated with the Immune-Suppressive Microenvironment and Unfavorable Prognosis in Pan-Cancer

J Inflamm Res. 2023 Mar 27:16:1375-1391. doi: 10.2147/JIR.S398284. eCollection 2023.

Authors

Xinwei Zhou^#¹, Ke Lin^#², Liangmin Fu^#¹, Fei Liu^#³, Hansen Lin¹, Yuhang Chen¹, Bowen Zhuang², Hui Liang⁴, Qiong Deng⁴, Zhu Wang⁴, Wei Chen¹, Junhang Luo^{1

5}, Jiazheng Cao⁶, Pengju Li¹

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
² Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
³ Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
⁴ Department of Urology, Affiliated Longhua People's Hospital, Southern Medical University, Shenzhen, People's Republic of China.
⁵ Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
⁶ Department of Urology, Jiangmen Central Hospital, Jiangmen, People's Republic of China.

^# Contributed equally.

Abstract

Background: Triggering receptors expressed by myeloid cells-1 (TREM1) is a receptor belonging to the immunoglobulin superfamily and plays an important role in pro-inflammation in acute and chronic inflammatory disorders. However, the understanding of the immunomodulatory roles of TREM1 in the tumor microenvironment remains incomplete.

Methods: The expression patterns of TREM1 mRNA in tumors and adjacent normal tissues were compared by analyzing data obtained from the Genotype-Tissue Expression and The Cancer Genome Atlas datasets. Survival analysis was performed to determine the prognostic value of TREM1. Functional enrichment analysis was applied to decipher the discrepancy in biological processes between high- and low-TREM1 groups across various cancers. The correlation between TREM1 and immune cell infiltration determined by using multiple algorithms was evaluated with the Pearson method. Four independent immunotherapy cohorts were adopted to validate the role of TREM1 as a biomarker.

Results: TREM1 was elevated in most cancers as verified with clinical samples. Overexpression of TREM1 was linked with undesirable prognosis in patients. Further analysis revealed that TREM1 was positively correlated with immune response, pro-tumor pathways, and myeloid cell infiltration, while being negatively correlated with CD8⁺ T cell (including infiltration level and biological processes). Concordantly, tumors with high TREM1 levels were more resistant to immunotherapy. Through connective map analysis, therapeutically potential compounds like tozasertib and TPCA-1 were identified, which can be used synergistically with immunotherapy to improve the poor prognosis of patients with high TREM1 levels.

Conclusion: Through a systematic and comprehensive pan-cancer analysis, we demonstrated that overexpression of TREM1 in tumors correlated closely with unfavorable outcome, infiltration of immune-suppressive cells, and immune regulation, which highlights its potential use as a tumor prognostic biomarker and a novel target for immunotherapy.

Keywords: clear cell renal cell carcinoma; immunotherapy; pan-cancer; prognostic biomarker; triggering receptors expressed by myeloid cells-1; tumor microenvironment.

Grants and funding

This work was supported by The National Science Fund for Distinguished Young Scholars of China (No.81725016), and The National Natural Science Foundation of China (No.81872094, No.82272862).