GABPA Expression in Endometrial Carcinoma: A Prognostic Marker

Abstract

Background. GA-binding protein A (GABPA), a transcription factor, is broadly involved in physiological and pathological processes. Several studies have investigated the relationship between GABPA expression level and outcomes of various malignancies. However, the function and clinicopathological significance of GABPA in endometrial carcinoma (EC) remain obscure. Methods. The GABPA mRNA expression in EC tissues and adjacent nonneoplastic tissues in the TCGA database was involved in our study. The protein expression of GABPA in 107 EC tissues and 15 normal endometrial tissues was detected by immunohistochemistry. Results. The GABPA expression was significantly downregulated in EC tissues compared with its expression in normal tissues ( $P<0.001$ ). The expression of GABPA was markedly correlated with type II EC ( $P<0.01$ ) and grade 3 EC ( $P<0.05$ ). A tendency has been observed that patients with low GABPA levels had relatively poorer overall survival (OS) ( $P=0.036$ ) and disease-free survival (DFS) ( $P=0.016$ ) than patients with high GABPA levels. The multivariate Cox proportional hazard model showed that lower expression of GABPA was an independent poor prognostic factor for OS ( $P=0.043$ ) and DFS ( $P=0.045$ ). Similar correlation between low expression levels of GABPA and unfavorable prognosis has also been found in type II or grade 3 EC. IHC analysis showed EC tissues had low expression of GABPA, which indicated relatively poor prognosis. Moreover, we identified that the GABPA mRNA expression was negatively correlated with its methylation level ( $R=-0.2512$ , $P<0.001$ ) which is one of the mechanisms for the silencing of GABPA gene. Conclusion. GABPA may act as an independent predictor of clinical prognosis and serve as a potential target gene for EC therapy.