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.

Crucial role of lncRNA NONHSAG037054.2 and GABPA, and their related functional networks, in ankylosing spondylitis

“…GABPA is a transcription factor in the ETS family ( 45 ) that is involved in the nuclear control of mitochondrial function and the expression of cytochrome oxidase c ( 46 , 47 ). Recent studies have indicated that GABPA is downregulated in clear cell renal cell carcinoma ( 48 ), endometrial carcinoma ( 49 ) and gastric cancer ( 50 ), and that high GABPA expression is associated with a lower survival rate of patients. In follicular thyroid carcinoma (FTC), GABPA directly regulates the expression of DICER1 and was also downregulated in clinical FTC samples ( 51 ).…”

hsa_circ_0006677 suppression of stemness and progression of non-small cell lung cancer by sponging miR-1276-induced ferroptosis in lung cancer stem cells

“…Deeper mining of the database and multiple examinations of clinical cohort 1 patients, LCSCs, and in vitro heterogeneous tumor model mice led us to identify an additional upstream transcription factor GABPA of hsa_circ_0006677. It has been demonstrated that GABPA levels in uence prognostic overall survival and disease-free survival and can be used as an independent predictor of clinical prognosis in endometrial cancer [34]. GABPA directly regulates DICER1 in follicular thyroid cancer, which acts as a tumor suppressor and is shown to be downregulated in clinical samples.…”

TERT promoter mutations and methylation for telomerase activation in urothelial carcinomas: New mechanistic insights and clinical significance

“…Intriguingly, GABPA and TERT expression even anti-correlated with each other in these tumors, suggesting a more complicated in vivo relationship between them ( 59 ). Like other tumor suppressors, the aberrant promoter hypermethylation and/or copy number loss contribute to the downregulation of GABPA or GABPB1 in the cancer types above ( 56 , 59 – 61 ). Collectively, GABPA and GABPB1 functions are context- or cell type-dependent, and caution should be taken to target them for telomerase-based cancer therapy.…”

“…Indeed, following stable GABPB1 knockdown, glioblastoma cells carrying C228T or C250T TERT promoters undergo diminished TERT/telomerase expression, progressive telomere erosion and eventual loss of tumorigenic potential (55). However, GABPA and GABPB1 stimulate TERT transcription, but several lines of evidence suggest that they may serve as tumor suppressors in other cancer types regardless the presence or absence of TERT promoter mutations (56,(58)(59)(60)(61)(62)(63). In UCBs, TCs and renal cell carcinomas (RCCs), GABPA or GABPB1 inhibition promotes their stemness and invasiveness, despite downregulation of TERT expression (59, 60, 63).…”