干扰素α诱导蛋白27在结直肠癌中的空间表达特征及其与CD8⁺ T细胞浸润的关系OA

Objective:Colorectal cancer(CRC)is one of the most common gastrointestinal malignancies worldwide,with high incidence and mortality rates.Its initiation and progression are regulated by the tumor microenvironment.Interferon alpha-inducible protein 27(IFI27)plays an important role in tumor immune evasion and microenvironmental remodeling;however,its spatial distribution pattern in CRC tissues and its interaction with CD8⁺ T cell infiltration remain incompletely understood.This study aims to investigate the spatial expression characteristics of IFI27 in CRC and to elucidate its association with the density of CD8⁺ T cell infiltration in the tumor microenvironment. Methods:A retrospective cohort study was conducted involving 65 CRC patients who underwent surgical resection.Tumor tissues and paired normal intestinal mucosal tissues were collected to construct tissue microarrays.Immunohistochemical(IHC)staining was performed to detect IFI27 and CD8A expression.QuPath digital pathology analysis software was used for single-cell-level quantification.Tissue regions were accurately segmented into epithelial and stromal compartments using a random forest algorithm.The histochemical score(H-score,0 − 300)was calculated based on mean optical density to quantify IFI27 protein expression,and CD8⁺ T cell infiltration was quantified according to cell density.The relative tumor-to-normal(T/N)expression ratio of IFI27 was calculated to minimize baseline heterogeneity.Correlation analyses were performed between IFI27 expression and clinicopathological parameters,including tumor invasion depth(T stage),lymph node metastasis status(N stage),and tumor size. Results:Spatial expression differences:IFI27 expression was significantly higher in epithelial regions than in stromal regions within CRC tissues(P<0.001).IFI27 expression levels in the whole tumor tissues,epithelial compartments,and stromal compartments were significantly higher than those in normal intestinal tissues(P=0.006,P=0.025,and P=0.016,respectively).The overall density of CD8⁺ T cell infiltration in the tumor microenvironment was significantly lower than that in normal tissues(P<0.001).Association with clinicopathological characteristics:IFI27 expression in tumor tissues was positively correlated with tumor size(Spearman r=0.322,P=0.015).CD8⁺ T cell infiltration density in the tumor microenvironment showed a decreasing trend with increasing tumor size(P=0.092).Differences according to metastatic status:The density of intratumoral CD8⁺ T cell infiltration was significantly higher in patients without lymph node metastasis(N⁻)than in those with lymph node metastasis(N ⁺)(P=0.026).This finding was consistently validated using the external Cancer Genome Atlas(TCGA)cohort(P=0.032).Dynamic correlations and survival analysis:In early-stage(T1 − 2)patients,CD8 ⁺ T cell infiltration density showed a positive correlation trend with the relative expression of IFI27(Spearman r=0.667,P=0.059).No correlation was observed in N⁻ patients with T3−4 disease(Spearman r=0.049,P=0.803).In contrast,a positive correlation between CD8+T cell infiltration density and the IFI27 T/N relative expression ratio was observed in N+patients with T3−4 disease(Spearman r=0.452,P=0.045).Survival analysis based on the TCGA cohort demonstrated that,in a combined cohort consisting of patients with T1−2 disease and N+T3 − 4 disease,high IFI27 expression was significantly associated with longer overall survival(OS)(P=0.004),whereas this association was not observed in N ⁻ patients with T3−4 disease(P=0.513). Conclusion:IFI27 exhibits preferential overexpression in CRC epithelial compartments and shows a positive association with CD8 ⁺ T cell infiltration in patients with early-stage CRC and those with advanced CRC accompanied by lymph node metastasis.