Abstract
Because the incidence of endometrial cancer is notably increasing worldwide, it has become the leading gynecologic cancer in the United States. Standard treatment results in the loss of reproductive function in women of childbearing age. Furthermore, advanced cancer stages are associated with poor overall survival. The aim of this study was to explore the abnormal expression profile of genes during the development of endometrial cancer, which is essential to provide a better understanding of the mechanisms involved. Five pairs of endometrial cancer tissues and normal endometrial tissues were subjected to next-generation transcriptome sequencing technology. Quantitative real-time PCR (RT-qPCR) was performed to validate the expression profile of key differentially expressed genes (2.0-fold change, adj. p < 0.05) (DEGs) identified in the RNA-seq result. GO and KEGG pathways were used for bioinformatic analyses. The transcriptomic sequencing results showed 1153 DEGs, including 673 upregulated and 480 downregulated genes, in the EC specimens. Decreased expression of ID1, IGF1, GDF7, SMAD9, TGF-beta and WNT4, as well as GDF5, INHBA and ERBB4 overexpression, were confirmed in EC using RT-qPCR. Additionally, EC tissue exhibited marked enrichment in genes promoting cellular adhesion, proliferation, migration and plasma membrane. KEGG analysis revealed changes in various pathways, such as the TGF-beta, PI3K-Akt, Wnt, and estrogen pathways. Our data describe the molecular events involved in the pathogenesis of EC, which may be potential diagnostic markers and targets of therapeutic interventions.
Highlights
According to China National Cancer Center in 2019, the incidence of endometrial cancer in China was 10.28/100,000, and the mortality rate was 1.9/100,000
PCNA expression was found to be related to pathogenesis and prognosis of endometrial cancer (EC) patients
The standard of care for these patients includes total hysterectomy (TH) and bilateral salpingo-oophorectomy (BSO) with selective use of pelvic and/ or para-aortic lymph node dissection depending on the risk factors and cancer staging (Koh et al, 2018)
Summary
According to China National Cancer Center in 2019, the incidence of endometrial cancer in China was 10.28/100,000, and the mortality rate was 1.9/100,000. In the USA, approximately 110,070 new cases of endometrial cancer (EC) were diagnosed in 2018, and it is considered the fourth most common type of cancer after breast, lung and colorectal carcinoma (Lortet-Tieulent et al, 2018; Siegel et al, 2021). Integrated Transcriptome in Endometrial Cancer as excessive exposure of the endometrium to estrogen, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility and polycystic ovary syndrome, have been associated with the onset of EC. 75% of women presenting with early-stage endometrial cancer could be taken under consideration with strict indications and follow-up for fertility-sparing treatment (McKenzie et al, 2018). Advanced stages of EC may result in a poor prognosis; early detection and treatment is the primary strategy for managing endometrial cancer
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