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Introduction
Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies worldwide [1, 2]. Advancements in diagnostic technologies and treatment strategies have improved survival rates among CRC patients [3]. However, significant tumor heterogeneity and complex microenvironments continue to pose considerable challenges to precision medicine [4]. In particular, the interactions and dynamic changes among various cell types within the TME profoundly influence tumor initiation, progression, and responses to immunotherapy [5].
In recent years, immune cells within the tumor immune microenvironment, especially macrophages and T cells, have emerged as critical focal points in the study of tumor immune evasion and anti-tumor immune responses [6, 7]. Research has shown that tumor-associated macrophages (TAMs) not only promote the proliferation and migration of tumor cells but also weaken the host’s anti-tumor immunity by affecting T cell activity [8, 9]. Therefore, understanding the mechanisms by which TAMs operate within the tumor microenvironment, particularly their association with tumor progression, has become a vital direction for exploring novel immunotherapeutic targets [10].
The development of single-cell RNA sequencing (scRNA-seq) technology has enabled researchers to conduct more precise analyses of tumors and their surrounding microenvironments. This technology reveals the heterogeneity of different cell populations, traces their developmental trajectories, and aids in identifying key genes critical to tumor growth [11, 12]. Among these, VSIG4 has garnered significant attention as a membrane protein that is highly expressed in tumor-associated macrophages [13]. As a member of the B7 family, VSIG4 (V-set Immunoglobulin-domain Suppressor of T cell Activation) was initially identified as a suppressive molecule involved in regulating innate immune responses [14]. Increasing evidence suggests that VSIG4 not only promotes immune evasion by inhibiting T cell activation but also influences immune responses within the tumor microenvironment through the modulation of macrophage function [15]. Abnormal expression of VSIG4 has been closely linked to immune evasion and poor prognosis in various cancer types, including CRC [16]. However, the specific mechanisms by which VSIG4 operates within the CRC tumor microenvironment remain insufficiently elucidated.
To further understand the biological functions and clinical significance of VSIG4 in CRC, this study comprehensively utilized the TCGA-COAD dataset and GEO database, integrating multi-omics and single-cell RNA sequencing data. We systematically investigated the expression patterns of VSIG4 within the tumor microenvironment and its association with macrophage...