杆状病毒凋亡抑制蛋白5在卵巢浆液性癌中的表达及意义

Expression and significance of baculovirus apoptosis inhibitor protein 5 in ovarian serous carcinoma

  • 摘要:
    目的 探讨杆状病毒凋亡抑制蛋白5(BIRC5)作为卵巢浆液性癌临床诊断和预后判断标志物的可能性及其潜在的作用机制。
    方法 从GEO数据库中下载GSE73638、GSE27651、GSE14001数据集, 应用GEO2R在线分析工具筛选差异表达基因(DEGs), 并对重叠DEGs进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过String数据库构建蛋白质-蛋白质相互作用(PPI)网络,应用Cytoscape软件分析PPI网络中的关键基因,并通过GEPIA数据库分析关键基因与生存预后的关系。采用免疫组织化学法检测58例卵巢浆液性癌患者38例卵巢高级别浆液性癌(HGSOC)和20例卵巢低级别浆液性癌(LGSOC)癌组织与癌旁组织中BIRC5、Ki-67和TP53蛋白表达情况,并分析BIRC5表达与临床病理特征的相关性。
    结果 对重叠DEGs进行GO和KEGG富集分析显示, BIRC5是卵巢浆液性癌的关键基因; GEPIA数据库分析结果显示, BIRC5基因与卵巢癌患者总体生存情况相关,即BIRC5表达越高,患者生存周期越长。LGSOC患者癌组织的BIRC5蛋白阳性表达率与癌旁组织比较,差异无统计学意义(χ2=1.026, P=0.311);HGSOC患者癌组织的BIRC5蛋白阳性表达率高于癌旁组织,差异有统计学意义(χ2=44.333, P < 0.001)。BIRC5、TP53和Ki-67蛋白在HGSOC癌组织中高表达, 在LGSOC癌组织中低表达。卵巢浆液性癌患者BIRC5蛋白表达情况与年龄、国际妇产科联盟(FIGO)分期、Ki-67蛋白表达和病理类型相关(P < 0.05), 与TP53蛋白表达无关(P>0.05)。HGSOC患者的总体生存率低于LGSOC组,但差异无统计学意义(χ2=3.522, P=0.061)。
    结论 BIRC5是卵巢浆液性癌的关键基因,可作为该疾病临床诊断和生存预后判断的新指标; BIRC5属于促癌基因,可能通过调控Ki-67表达而非TP53信号通路促进卵巢浆液性癌的发生与发展。

     

    Abstract:
    Objective To investigate the possibility of baculovirus apoptosis inhibitor protein 5(BIRC5) as a clinical diagnostic and prognostic marker for ovarian serous carcinoma and its potential mechanism.
    Methods The GSE73638, GSE27651 and GSE14001 datasets were downloaded from the GEO database, and the differentially expressed genes (DEGs) were screened using the GEO2R online analysis tool. The protein-protein interaction (PPI) network was constructed using the String database, and key genes in the PPI network were analyzed using Cytoscape software. The relationship between key genes and prognosis was analyzed in the GEPIA database. Expressions of BIRC5, Ki-67 and TP53 proteins in cancer and adjacent tissues in 58 clinical cases38 cases of high-grade serous ovarian cancer (HGSOC) and 20 cases of low-grade serous ovarian cancer (LGSOC) were detected for correlation of BIRC5 expression with clinicopathological factors by immunohistochemical method.
    Results GO and KEGG enrichment analysis of overlapping DEGs showed that BIRC5 was a key gene in ovarian serous carcinoma. The results of GEPIA database analysis showed that BIRC5 gene was correlated with the overall survival of ovarian cancer patients, which indicated that the higher the expression of BIRC5 was, the longer the survival cycle of patients lasted. There was no significant difference in the positive expression rate of BIRC5 protein in para-cancer tissues of LGSOC patients(χ2=1.026, P=0.311). The positive expression rate of BIRC5 protein in cancer tissues of HGSOC patients was higher than that in adjacent tissues, the difference was statistically significant (χ2=44.333, P < 0.001). BIRC5, TP53 and Ki-67 proteins were highly expressed in HGSOC cancer tissues, but lowly expressed in LGSOC cancer tissues. BIRC5 protein expression was correlated with age, International Federation of Gynecology and Obstetrics (FIGO) stage, Ki-67 protein expression and pathological type (P < 0.05), but had no correlation with TP53 protein expression in patients with ovarian serous carcinoma (P>0.05). The overall survival rate of HGSOC patients was lower than that of LGSOC group, but the difference was not statistically significant (χ2=3.522, P=0.061).
    Conclusion BIRC5 is a key gene of ovarian serous cancer and can be used as a new index for clinical diagnosis and survival prognosis of the disease. BIRC5 is a pro-cancer gene, which may promote the occurrence and development of ovarian cancer by regulating the expression of Ki-67 rather than the signal pathway of TP53.

     

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