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OBJECTIVE: To analyze the p53, PKD1, and MAP2K4 expressions in serum of patients with endometrial carcinoma (EC) and their prognostic value. METHODS: A total of 84 patients with EC who were treated in our hospital between January 2018 and January 2020 were enrolled into a research group. There were 50 healthy individuals over the same time who were included in a control group for a retrospective analysis. qRT-PCR was used for quantifying the relative levels of p53, PKD1, and MAP2K4 in the serum of the control group and the research groups (in both cancer and paracancerous tissues). The associations of p53, PKD1, and MAP2K4 with pathological features of EC were analyzed. Patients were followed up for 1 year to observe their death and analyze the associations of p53, PKD1, and MAP2K4 with prognosis of EC. RESULTS: The patients with EC had low p53 and MAP2K4 levels and high PKD1 levels (P<0.05). The p53, MAP2K4, and PKD1 levels in serum were relevant to EC differentiation, FIGO stage, lymph node metastasis, and deep myometrial invasion (P<0.05). During the follow-up of prognosis, the serum levels of p53 and MAP2K4 in dead patients were lower than those in surviving patients. PKD1 in former patients was higher (P<0.05). CONCLUSION: The low expressions of p53 and MAP2K4 and high expression of PKD1 in EC cases were related with disease progression. These expressions can help effectively evaluate the prognosis and survival of patients. They are of crucial research and reference significance for future diagnosis and therapy.
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BACKGROUND: Endometrial carcinoma (EC) has become a common gynecologic malignancy with a high mortality. The m6A regulators have been identified to be closely associated with multiple human cancers including EC. However, the CpG methylation signature related to m6A regulators in EC remains unclear. METHOD: The methylation profiles of EC patients including cancer samples and adjacent normal samples were obtained from The Cancer Genome Atlas (TCGA) database. The CpG sites in 20 m6A regulators were identified. Univariate Cox regression and LASSO Cox regression analysis were used to screen key CpG sites which were located at m6A regulators and significantly related to the prognosis of EC. The predictive model for EC prognosis was constructed, and multivariate Cox regression analysis was applied to explore whether the risk score derived from the model could function as an independent signature for EC prognosis. Meanwhile, a nomogram model was constructed by combing the independent prognostic signatures for prediction of the long-term survival in EC patients. RESULTS: A total of 396 CpG sites located at 20 m6A regulators were identified. A specific predictive model for EC prognosis based on 7 optimal CpG sites was constructed, which presented good performance in prognosis prediction of EC patients. Moreover, risk score was determined to be an independent signature both in the training set and validation set. By bringing in three independent prognostic factors (age, risk score, and TNM stage), the nomogram was constructed and could effectively predict the 3- and 5-year survival rates of EC patients. CONCLUSION: Our study suggested that the CpG sites located at m6A regulators might be considered as potential prognostic signatures for EC patients.
Subject(s)
Adenosine/analogs & derivatives , Endometrial Neoplasms/mortality , Adenosine/genetics , Adenosine/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , China , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Methylation , Middle Aged , Nomograms , Predictive Value of Tests , Prognosis , Proportional Hazards Models , RNA/genetics , Survival AnalysisABSTRACT
BACKGROUND: Endometrial cancer (EC) is the sixth most common cancer in women globally. It has been found that the expression levels of m6A regulators can be potentially used for prognostic stratification in some cancers, but the role of m6A regulators in EC prognosis remains unclear. METHODS: The data of 584 EC samples were downloaded from The Cancer Genome Atlas and the mRNA expression profiles of 20 m6A regulators were analyzed, followed by functional enrichment analysis, immune infiltration analysis, and least absolute shrinkage and selection operator method-COX regression analysis. RESULTS: The mRNA expression levels of 20 m6A regulators were significantly different between cancer samples across different grades. The 548 EC samples could be clearly divided into 2 clusters. Kaplan-Meier survival analysis proved that these two groups had highly different overall survival probabilities. Besides, the univariate regression analysis further reserved eight genes related to overall survival from the 20 m6A regulators. We established a prognostic signature including two genes, that is, IGF2BP1 and YTHDF3, that showed a strong ability for stratifying prognostically different EC patients. We identified 3239 differentially expressed genes between the high- and low-risk groups, involving in multiple biological processes and signaling pathways. Meanwhile, 6 differentially infiltrated immune cell types between the high- and low-risk groups could effectively distinguish the high- and low-risk EC groups. The expressions of immune checkpoints were different between high- and low-risk EC patients. CONCLUSION: We first report the prognostic role of m6A regulators in EC, which should contribute to a better understanding of the underlying mechanisms of EC pathogenesis and progression.
