Clinics (Sao Paulo, Brazil) · 2025
The role of SIGLEC9 in immunosuppression and prognosis in cervical cancer.
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Wang Bihui, Zhu Yuejie, Ru Zhenyu, Zhang Yulian, Yu Mingkai, Li Pingfen, Zhang Manli, Ding Jianbing, Chen Zhifang
Аннотация
OBJECTIVE: This study investigates the role of Sialic acid-binding Immunoglobulin-Like Lectin-9 (SIGLEC9), a novel immune checkpoint, in Cervical Cancer (CC) and its interaction with immune cells in the tumor microenvironment.
METHODS: SIGLEC9 expression in CC was analyzed using the TNM plot, TCGA, and Human Protein Atlas databases, alongside its correlation with tumor stage. The relationship between SIGLEC9 expression and immune cell infiltration was explored using TCGA and TISIDB databases. Single-cell analysis focused on SIGLEC9 in macrophages. Protein interactions were assessed through the String, IntAct, BioGRID, and Mentha databases. MUC1 expression was validated via GEO and GEPIA databases. Immunohistochemical staining, western blot, immunofluorescence, and flow cytometry were used for verification. The prognostic significance of SIGLEC9 and SIGLEC9+ Tumor-Associated Macrophages (TAMs) was evaluated.
RESULTS: SIGLEC9 was found to be significantly upregulated in CC, with higher levels correlating with poor prognosis. It was expressed in macrophages and T-cells, and elevated SIGLEC9+ TAMs were linked to reduced overall survival.
CONCLUSION: SIGLEC9 plays a crucial role in the progression and prognosis of cervical cancer through its interaction with TAMs and T-cells. These findings highlight SIGLEC9 as a potential target for new immunotherapies in CC.
METHODS: SIGLEC9 expression in CC was analyzed using the TNM plot, TCGA, and Human Protein Atlas databases, alongside its correlation with tumor stage. The relationship between SIGLEC9 expression and immune cell infiltration was explored using TCGA and TISIDB databases. Single-cell analysis focused on SIGLEC9 in macrophages. Protein interactions were assessed through the String, IntAct, BioGRID, and Mentha databases. MUC1 expression was validated via GEO and GEPIA databases. Immunohistochemical staining, western blot, immunofluorescence, and flow cytometry were used for verification. The prognostic significance of SIGLEC9 and SIGLEC9+ Tumor-Associated Macrophages (TAMs) was evaluated.
RESULTS: SIGLEC9 was found to be significantly upregulated in CC, with higher levels correlating with poor prognosis. It was expressed in macrophages and T-cells, and elevated SIGLEC9+ TAMs were linked to reduced overall survival.
CONCLUSION: SIGLEC9 plays a crucial role in the progression and prognosis of cervical cancer through its interaction with TAMs and T-cells. These findings highlight SIGLEC9 as a potential target for new immunotherapies in CC.