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.