Bioinformatics analysis of key differentially expressed genes in well and poorly differentiated endometrial carcinoma

Abstract

Endometrial carcinoma (EC) is one of the most common gynecological malignancies. The malignant degree increases between grade (G)1 and G3, and EC of G3 usually presents a high recurrence rate and poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in EC. The microarrays GSE17025, GSE24537 and GSE35784, representing data of Type I EC samples of G1 and G3, were downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) and differentially expressed micro (mi)RNAs (DEMs) were identified, followed by functional enrichment analyses and interaction network construction. In total, 83 upregulated and 130 downregulated DEGs with the same expression trends in two mRNA datasets were screened. The upregulated DEGs were primarily enriched in 'mitotic cell cycle process', 'cell cycle process' and 'mitotic cell cycle'; while the downregulated DEGs were enriched in 'cellular component assembly involved in morphogenesis', 'cell projection organization' and 'microtubule‑based movement'. From the protein‑protein interaction network, DNA topoisomerase IIα, kinesin family member 11, cyclin B1 and BUB1 mitotic checkpoint serine/threonine were identified as foremost hub genes. One module was extracted and involved in 'mitotic cell cycle process' and 'cell cycle process'. Based on the analysis of DEMs and the miRNA‑target regulatory network, miRNA‑9 may be the most important upregulated DEM, and the DEGs forkhead box P1 and cyclin E1 may serve vital roles in the differentiation of EC. In conclusion, principal genes were identified that may be determinants of the carcinogenesis of poorly differentiated EC, which may facilitate the examination of potential molecular mechanisms. These genes may additionally help identify candidate biomarkers and novel therapeutic targets for poorly differentiated EC.

Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools

“…Gene expression profiles revealed three distinctive gene clusters, with genes upregulated (clusters I and II) or downregulated (cluster III) in grade 3 tumors in comparison to grade 1 tumors. These results are in line with a recent study reporting the identification of genes and microRNAs (miRs) differentially expressed in grade 3 EC and functionally associated with cell cycle regulation ( 43 ).…”

Computational approaches for discovering significant microRNAs, microRNA-mRNA regulatory pathways, and therapeutic protein targets in endometrial cancer

“…We also discovered miRNA changes that target genes controlling the transformation of normal endometrial tissue to aggressive malignant ones. High estrogen level, overweight, diabetes mellitus and other human disorders that are known to raise the risk of endometrial cancer can be better understood by finding hub genes, with the highest degree of centrality in the key module ( Zang et al, 2018 ). Therefore, when generating miRNA-mRNA functional network that are composed of 66 miRNA target genes and 26 miRNAs, we identified 18 hub target genes and 5 miRNAs with a high degree of centrality parameter (>50).…”

Identification of a five‑gene signature for predicting the progression and prognosis of stage I endometrial carcinoma

“…The CCNB1 gene encodes an important regulator of the cell cycle and is associated with cyclin-dependent kinase 1, and it is also known to regulate the G 2 /M transition during mitosis (62). It has been previously reported that CCNB1 expression is associated with poorly differentiated EC (7). Integrated bioinformatics analysis methods were used to examine TCGA and GEO datasets (26).…”

“…High-grade stage I UCEC progresses rapidly and presents with a high metastatic rate within a short time (6). Higher-grade classification takes into account the number of tumor cells undergoing differentiation, which allows the more malignant biological behavior to be observed (7). High-grade UCEC frequently presents with lymph-vascular space invasion and deep myometrial infiltration (8).…”