SERPINB4在宫颈癌中的表达及其预后价值

Expression of SERPINB4 in Cervical Cancer and its Prognostic Value

目的探讨丝氨酸蛋白酶抑制剂B4(SERPINB4)在宫颈癌中的表达与预后相关性,分析其在宫颈癌中与肿瘤免疫浸润的关系。方法基于TCGA与GTEx数据库获取宫颈癌相关的表达数据和临床参数,分析SERPINB4在正常宫颈组织和宫颈癌组织中的表达水平与临床病理特征、肿瘤浸润免疫细胞,免疫检查点标志分子及对化疗药物敏感性之间的相关性。应用Kaplan-Meier生存分析方法与ROC曲线评估SERPINB4在宫颈癌中的预后价值,并将SERPINB4及其共同表达基因进行GO与KEGG富集分析,探讨SERPINB4在宫颈癌中可能调控的分子信号通路。结果SERPINB4在宫颈癌组织中呈高度表达(P<0.05);SERPINB4与宫颈癌患者不良预后(P=0.035)及远处转移(P=0.0092)相关;6个TIICs与SERPINB4表达呈正相关,其表达与多个免疫检查点存在统计学意义;SERPINB4在免疫细胞评分、基质细胞评分和综合评分较低组均升高,并且在宫颈癌患者中SERPINB高表达对靶向药物敏感性较差;GO分析发现SERPINB4及共表达基因多富集在免疫相关功能的调控,KEGG通路富集显示SERPINB4及共表达基因可能参与调控cAMP信号通路。结论与正常宫颈组织相比,在宫颈癌组织中SERPINB4的高表达与患者预后不良及肿瘤免疫浸润有关,SERPINB4可能是宫颈癌的预后分子标志物和潜在的免疫治疗靶点。

Objective To explore the correlation between the expression of serine protease inhibitor B4(SERPINB4)in cervical cancer and prognosis,and analyze its relationship with tumor immune infiltration in cervical cancer.Methods The expression data and clinical parameters related to cervical cancer were obtained based on TCGA and GTEx databases.The correlation between the expression level of SERPINB4 in normal cervical tissues and cervical cancer tissues and clinicopathological features,tumor infiltrating immune cells,immune checkpoint marker molecules and sensitivity to chemotherapeutic drugs was analyzed.Kaplan-Meier survival analysis and ROC curve were used to evaluate the prognostic value of SERPINB4 in cervical cancer.GO and KEGG enrichment analysis of SERPINB4 and its co-expressed genes were performed to explore the molecular signaling pathways that SERPINB4 might regulate in cervical cancer.Results SERPINB4 was highly expressed in cervical cancer tissues(P<0.05).SERPINB4 was associated with poor prognosis(P=0.035)and distant metastasis(P=0.0092).Six TIICs were positively correlated with SERPINB4 expression,and their expression was statistically significant with multiple immune checkpoints.SERPINB4 was increased in the lower immune cell score,stromal cell score and comprehensive score group,and the high expression of SERPINB in cervical cancer patients was less sensitive to targeted drugs.GO analysis showed that SERPINB4 and co-expressed genes were mostly enriched in the regulation of immune-related functions.KEGG pathway enrichment showed that SERPINB4 and co-expressed genes might be involved in the regulation of cAMP signaling pathway.Conclusion Compared with normal cervical tissues,the high expression of SERPINB4 in cervical cancer tissues is related to poor prognosis and tumor immune infiltration.SERPINB4 may be a prognostic molecular marker and potential immunotherapy target for cervical cancer.