Expression of immunoglobulin superfamily member 9 in endometrial carcinoma and its association with prognosis and immune characteristics

ZHU Yufen; QIN Fengxia; XU Leichan; BI Kehao; SONG Chunhong

doi:10.3969/j.issn.1009-0460.2025.10.006

Abstract：Objective To investigate the expression of immunoglobulin superfamily member 9(IGSF9)in endometrial carcinoma(EC)and its relationship with prognosis and immune cell infiltration.Methods A total of 106 EC patients who underwent radical surgery at the Fourth Hospital of Shijiazhuang between January 2016 and December 2019 were enrolled.From the surgical specimens,106 tumor tissues and 58 paired adjacent normal endometrial tissues were collected for the study.Immunohistochemistry(IHC)was used to detect the expression level of IGSF9 in tissues,and its relationship with clinicopathological characteristics was evaluated.The Gene Expression Profiling Interactive Analysis(GEPIA)database was employed to analyze IGSF9 mRNA expression.Real-time quantitative PCR(RT-qPCR)and Western blot were performed to determine mRNA and protein expression levels of IGSF9,respectively.Kaplan-Meier survival analysis with the log-rank test and Cox proportional hazards regression models were applied to assess the association between IGSF9 expression and patient prognosis.The Tumor Immune Estimation Resource(TIMER)database was utilized to explore the relationship between IGSF9 expression and immune cell infiltration.Results Immunohistochemical analysis revealed a positive expression rate of IGSF9 protein in EC tissues of 55.7%(59/106),significantly higher than the 20.7%(12/58)observed in adjacent non-cancerous tissues,with a statistically significant difference(P<0.001).Moreover,high IGSF9 expression was closely associated with adverse clinicopathological features,including lymph node metastasis,advanced(Stage Ⅲ and Ⅳ)FIGO staging,and deep myometrial invasion.Validation via the GEPIA database,RT-qPCR,and Western blot experiments consistently demonstrated that both mRNA and protein expression levels of IGSF9 were significantly elevated in EC tissues compared to normal tissues(all P<0.01).Survival analysis indicated that the median overall survival of IGSF9-positive patients was 44 months,significantly shorter than the 57 months in the IGSF9-negative group,with a statistically significant difference(P=0.001).Multivariate analysis confirmed that IGSF9 positivity is an independent significant risk factor for patient prognosis,with a hazard ratio of 5.684(P=0.039),indicating that the risk of death in positive patients was 5.684 times that of negative patients.Furthermore,analysis of the TIMER database revealed that IGSF9 expression was significantly negatively correlated with the infiltration levels of B cells,CD8⁺ T cells,CD4⁺ T cells,macrophages,and dendritic cells in the tumor microenvironment(all P<0.05).Conclusion IGSF9 is highly expressed in EC,and its expression level is associated with poor patient prognosis and an immunosuppressive microenvironment,suggesting its potential as a biomarker for prognostic assessment and a target for immunotherapy in EC.