Deciphering the Molecular and Clinical Characteristics of Trem2, Hcst, and Tyrobp in Cancer Immunity: A Comprehensive Pan-Cancer Study

Abstract

Background: Triggering receptor expressed on myeloid cells 2 (TREM2), hematopoietic cell signal transducer (HCST), and TYRO protein tyrosine kinase-binding protein (TYROBP) serve as pivotal elements within the immune response to disease. Despite growing evidence underscoring the significance of TREM2, HCST, and TYROBP in certain forms of tumorigenesis, a comprehensive pan-cancer analysis of these elements remains absent.

Methods: A synthesis of multiple databases facilitated an investigation into the relationship between the expression of TREM2, HCST, and TYROBP and various cancer types. This encompassed factors such as prognosis, methylation, regulation by long non-coding RNAs and transcription factors, immune signatures, pathway activity, microsatellite instability (MSI), tumor mutational burden (TMB), single-cell transcriptome profiling, and drug sensitivity.

Results: TREM2, HCST, and TYROBP displayed extensive somatic changes across numerous tumors, with their mRNA expression and methylation levels influencing patient outcomes across multiple cancer types. lncRNA-mRNA and TF-mRNA regulatory networks involving TREM2, HCST, and TYROBP were identified, with lncRNA MEG3 and transcription factor SIP1 emerging as potential key regulators. Further immune analyses indicated that TREM2, HCST, and TYROBP play critical roles in immune-related pathways and macrophage differentiation and may have a significant association with TGF-β and SMAD9. Furthermore, the expressions of TREM2, HCST, and TYROBP correlated with immunotherapy markers TMB and MSI and influenced the sensitivity to immune-targeted drugs, thereby indicating potential as predictors of immunotherapy outcomes.

Conclusion: This study offers valuable insights into the roles of TREM2, HCST, and TYROBP in tumor immunotherapy, suggesting their potential as both prognostic markers and therapeutic targets across various cancers.

Note:
Funding declaration: This work was supported by Hunan Cancer Hospital Climb Plan (No. IIT2021001), Science and Technology Program of Henan, China (No.192102310161 and NO.182102310291) and Hunan Provincial Education Commission Foundation (No.19B068, No.20A056).

Conflict of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Keywords: triggering receptor expressed on myeloid cells 2 (TREM2), hematopoietic cell signal transducer (HCST), TYRO protein tyrosine kinase-binding protein (TYROBP), pan-cancer, tumor immunity.