BTG1 inhibits malignancy as a novel prognosis signature in endometrial carcinoma

Abstract

Background Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC. Methods Based on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Results We analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs. Conclusions BTG1, as a tumor suppressor gene, plays an important role in the occurrence and development of EC. We believe that BTG1 can be used as a potential prognostic biomarker for EC.

Recent Multiomics Approaches in Endometrial Cancer

“…Another study based on RNA-seq data reported that 542 patients had high RNF183 expression, which was associated with favorable overall survival and progression-free survival [48]. It was similar in the study by Li et al, where higher OS was noted in patients with high BTG1 expression [50]. In turn, high expression of HOXB9 and E2F3 correlated with a shorter survival time [51].…”

“…In a recent endometrial cancer study, 581 TCGA tissue samples, including 546 EC samples and 35 normal endometrial samples, were used during analysis. Expression of TMEFF2 [47] and BTG anti-proliferation factor 1 (BTG1) [50] was lower in primary endometrial cancer compared to the healthy endometrium, while significant overexpression was noted for ring finger protein 183 (RNF183) [48]. In turn, the ZBTB7A expression was low in endometrial cancer tissues grouped according to cancer stage, age, and race compared to the control group [49].…”

“…Interestingly, the expression of RNF183 and BTG1 was higher in endometrioid EC compared to the non-endometrioid subtypes. In addition, analyses using the Oncomine database also allowed observing a high expression of RNF183 and BTG1 in TP53-Non-Mutant EC compared to TP53-Mutant EC [48,50].…”

“…The analysis performed for the BTG1 gene revealed strong correlations between the expression of BTG1 and SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL), protein-L-isoaspartate O-methyltransferase domain-containing protein 1 (PCMTD1), and tetmethylcytosine dioxygenase 2 (TET2). Moreover, taking into account the top 50 gene sets related to BTG1, their functions include the regulation of cell cycle, apoptosis, and carcinogenesis [50].…”

“…In recent endometrial cancer research, the LinkedOmics database has been used to find networks of miRNA targets, as was already described in detail [47,48]. In addition, Li et al used the miRDB database (http://mirdb.org) (accessed on 1 December 2021) in their study, as it allows the prediction of miRNA targets and functional annotation [50,73]. The aim of the study was to select miRNAs that can bind to BTG1.…”