A Risk Signature with Nine Stemness Index-Associated Genes for Predicting Survival of Patients with Uterine Corpus Endometrial Carcinoma

Abstract

Purpose. To identify mRNA expression-based stemness index- (mRNAsi-) related genes and build an mRNAsi-related risk signature for endometrial cancer. Methods. We collected mRNAsi data of endometrial cancer samples from The Cancer Genome Atlas (TCGA) and analyzed their relationship with the main clinicopathological characteristics and prognosis of endometrial cancer patients. We screened the top 50% of the genes in TCGA for weighted gene correlation network analysis (WGCNA) to explore mRNAsi-related gene sets. Among these mRNAsi-related genes, we further screened for those related to the prognosis of endometrial cancer patients via univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Using stepwise multivariate Cox regression analysis, a stemness index-related risk signature was constructed. Finally, we identified potential prognostic biomarkers for endometrial cancer by combining the GEO database and immunohistochemical staining. Results. The mRNAsi of endometrial cancer samples was significantly higher than that of normal samples and was related to the International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, postoperative tumor status, and overall survival of endometrial cancer patients. We identified 21 mRNAsi-related gene modules, and 1,324 genes were obtained from the most relevant module. TCGA samples were divided into training and validation cohorts, and the training cohort was used to construct a nine-mRNAsi-related gene signature (B3GAT2, CD3EAP, DMC1, FRMPD3, LINC01224, LINC02068, LY6H, NR6A1, and TLE2). High-risk and low-risk patients had significant prognostic differences, and the risk signature could accurately predict their 1-, 3-, and 5-year survival. The nomogram composed of risk score and multiple clinicopathological features could accurately predict 1-, 3-, and 5-year survival. Finally, CD3EAP was found to be a novel prognostic biomarker for endometrial cancer. Conclusion. Endometrial cancer cell stemness is related to patient prognosis. The nine-gene risk signature is an independent prognostic factor and can accurately predict endometrial cancer patient prognosis.

Development of an Oxidative Phosphorylation-Related and Immune Microenvironment Prognostic Signature in Uterine Corpus Endometrial Carcinoma

“…We compared the MSI status of different risk groups and found that the expression of dominant MMR proteins (MLH1, MSH2, MSH6, PMS2, and EPCAM) and mRNAsi in the low-risk group was downregulated, which illustrated that the patients with low risk score were burdened with high-MSI and showed fewer stemness features associated with oncogenic dedifferentiation. Haoya Xu et al found that cell stemness can predict patient prognosis and constructed an mRNAsi-related prognostic signature in endometrial cancer ( Xu et al, 2021 ). Accumulating evidence revealed that m 6 A mRNA methylation participates in the pathogenesis and progression of cancers through molecular mechanisms, such as inhibiting the antitumor response of CD8 + T cells ( Chen et al, 2019 ; Sun et al, 2019 ).…”

Integration of Transcriptome and Epigenome to Identify and Develop Prognostic Markers for Ovarian Cancer

“…The protein encoded by DMC1, a member of the Recombinases superfamily, is essential to repair double-stranded DNA breaks during mitosis and meiosis [ 27 , 28 ]. It is also strongly correlated with the prognosis of patients with endometrial cancer [ 29 ] and is downregulated in OV tissues [ 30 ]. The protein encoded by TCIRG1 is a subunit of H+-ATPase, and a prognostic marker and immune infiltration marker in patients with glioma [ 31 ].…”

Development and Validation of a RNA Binding Protein-Associated Prognostic Model for Uterine Corpus Endometrial Carcinoma

“…Studies have shown that CD3EAP affects the transcription process of rRNA and the activity of RNA polymerases, and participates in the proliferation process of cells, CD3EAP can also mediate the activation pathway of T cells to produce leukocyte interleukin-2 to inhibit the growth of cancer cells [22,23]. In the study of Haoya Xu et al, they nd that the high expression of CD3EAP in endometrial cancer was related to a higher pathological grade, later clinical stage, and postoperative tumor recurrence [24]. And it has also been found to be one of the genes with the highest mutation rate in hepatoid adenocarcinoma of the stomach [25].…”

“…In addition, there are some limitations to our study when interpreting the results. As the two validation groups in this trial were randomly divided into test groups, the prognostic information of endometrial cancer patients was not available in other databases such as GEO and ICGC, which we could not validate using external datasets [44], and some important clinical characteristics of UCEC patients, such as living environment and family history, were missing from the TCGA database, and in future studies, more uterine endometrial samples and detailed clinical information for validation in future studies.…”