【摘要】 目的 通过检测正常子宫内膜组织、子宫内膜癌肿瘤组织中SLC7A11(溶质载体家族7成员11)表达水平，结合临床资料及生物信息学，探讨在子宫内膜癌发生及疾病进展过程中，SLC7A11表达水平的临床意义。方法 本研究选取93例子宫内膜癌组织，21例正常子宫内膜组织。其利用免疫组化染色技术检测各组组织中SLC7A11表达水平，分析SLC7A11表达与子宫内膜癌患者临床病理参数之间的关系，搜集93例子宫内膜癌患者随访资料并绘制无进展生存期(PFS)生存曲线。利用R语言将TCGA数据库中子宫内膜癌相关数据按SLC7A11表达量进行分组，筛选差异基因(DEGs)进行GO、KEGG、GSEA等富集分析，探究与SLC7A11可能相关的分子信号通路，同时利用ESTIMATE免疫算法及免疫检查点差异分析探究SLC7A11与子宫内膜癌免疫浸润及相关免疫检查点的关系。结果 免疫组化结果：与正常子宫内膜组织相比，子宫内膜癌肿瘤组织中SLC7A11蛋白表达水平明显升高(P<0.05);SLC7A11阳性表达与子宫内膜癌组织类型是否为侵袭性、临床分期、组织分化及患者BMI等临床病理特征有关(χ~2=7.0453、9.8403、15.752、5.0786,均P<0.05)。生存分析：SLC7A11表达水平对子宫内膜癌患者PFS无明显影响(P=0.526)。生物信息学分析：子宫内膜癌组织中SLC7A11表达水平显著高于子宫正常内膜组织(P<0.05);GO分析发现SLC7A11相关DEGs主要集中于上皮细胞增殖分化等生物过程，在肌钙蛋白复合体、角蛋白丝等细胞组分富集；KEGG分析发现SLC7A11相关DEGs主要富集于神经活性配体信号通路、cAMP信号通路等通路；GSEA分析发现mTORC1信号通路、G2/M期检查点、上皮-间质转化、P53信号通路等相关基因在子宫内膜癌SLC7A11高表达的人群中富集；SLC7A11高表达与滤泡辅助T细胞(Tfh)、活化记忆CD4~+T细胞、静息记忆CD4~+T细胞、静息NK细胞、活化肥大细胞、γδT细胞等免疫细胞浸润呈正相关，与浆细胞、活化NK细胞、静息肥大细胞、调节性T细胞(Tregs)等免疫细胞浸润呈负相关，SLC7A11的表达可能影响CD274、PDCD1LG2、CTLA4、HAVCR2等免疫检查点基因的表达。结论 SLC7A11在子宫内膜癌中高表达，可能参与子宫内膜癌的发生发展，在子宫内膜癌的发展过程中可能起到促进作用。生信分析提示SLC7A11可能影响子宫内膜癌免疫检查点基因的表达，成为预测子宫内膜癌后续进展和免疫治疗的指标，或能为针对SLC7A11高表达的子宫内膜癌患者进行免疫靶向治疗提供参考，可能成为子宫内膜癌治疗的潜在靶点。更多还原

【Abstract】 Objective To detect the expression levels of SLC7A11(solute carrier family 7 member 11) in normal endometrial tissues and endometrial cancer tumor tissues, and combine clinical data and bioinformatics to explore the clinical significance of SLC7A11 expression levels in the occurrence and progression of endometrial cancer.Methods This study selected 93 cases of endometrial cancer tissues and 21 cases of normal endometrial tissues. It utilized immunohistochemical staining techniques to detect the expression levels of SLC7A11 in each group of tissues, analyzed the relationship between SLC7A11 expression and the clinical pathological parameters of endometrial cancer patients, collected follow-up data of 93 endometrial cancer patients and drew the progression-free survival(PFS) survival curve. Using R,the endometrial cancer-related data in the TCGA database were grouped according to the expression level of SLC7A11,and the differentially expressed genes(DEGs) were screened for GO,KEGG,GSEA and other enrichment analyses to explore the possible molecular signaling pathways related to SLC7A11. At the same time, the ESTIMATE immune algorithm and immune checkpoint difference analysis were used to explore the relationship between SLC7A11 and immune infiltration and related immune checkpoints in endometrial cancer.Results Immunohistochemical results: compared with normal endometrial tissues, the expression level of SLC7A11 protein in endometrial cancer tumor tissues was significantly increased(P<0.05).The positive expression of SLC7A11 was related to the clinical pathological characteristics of endometrial cancer tissues, such as whether they were invasive, clinical stage, tissue differentiation, and patient BMI(χ~2=7.0453,9.8403,15.752,5.0786,all P<0.05).Survival analysis: the expression level of SLC7A11 had no significant effect on the PFS of endometrial cancer patients(P=0.526).Bioinformatics analysis: the expression level of SLC7A11 in endometrial cancer tissues was significantly higher than that in normal endometrial tissues(P<0.05). GO analysis found that SLC7A11-related DEGs were mainly concentrated in biological processes such as epithelial cell proliferation and differentiation, and were enriched in cellular components such as troponin complex and keratin filament.KEGG analysis found that SLC7A11-related DEGs were mainly enriched in signaling pathways such as neuroactive ligand-receptor interaction and cAMP signaling pathway. GSEA analysis found that genes related to mTORC1 signaling pathway, G2/M checkpoint, epithelial-mesenchymal transition, and P53 signaling pathway were enriched in the population with high expression of SLC7A11 in endometrial cancer. High expression of SLC7A11 was positively correlated with the infiltration of immune cells such as follicular helper T cells(Tfh),activated memory CD4~+ T cells, resting memory CD4~+ T cells, resting NK cells, activated mast cells, and γδT cells, and negatively correlated with the infiltration of immune cells such as plasma cells, activated NK cells, resting mast cells, and regulatory T cells(Tregs). The expression of SLC7A11 might affect the expression of immune checkpoint genes such as CD274,PDCD1LG2,CTLA4,and HAVCR2.Conclusion SLC7A11 is highly expressed in endometrial cancer and may be involved in the occurrence and development of endometrial cancer, possibly playing a promoting role in the development of endometrial cancer. Bioinformatics analysis suggests that SLC7A11 may affect the expression of immune checkpoint genes in endometrial cancer and may become an indicator for predicting the subsequent progression and immunotherapy of endometrial cancer, or provide a reference for immunotargeted therapy for endometrial cancer patients with high expression of SLC7A11,and may become a potential target for the treatment of endometrial cancer.更多还原