Abstract
BackgroundGlobally, endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Tumor progression is strongly related to the cell survival-promoting functions of autophagy. We explored the relationship between endometrial cancer prognoses and the expression of autophagy genes using human autophagy databases.MethodsThe Cancer Genome Atlas was used to identify autophagy related genes (ARGs) that were differentially expressed in endometrial cancer tissue compared to healthy endometrial tissue. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were referenced to identify important biological functions and signaling pathways related to these differentially expressed ARGs. A prognostic model for endometrial cancer was constructed using univariate and multivariate Cox, and Least Absolute Shrinkage and Selection Operator regression analysis. Endometrial cancer patients were divided into high- and low-risk groups according to risk scores. Survival and receiver operating characteristic (ROC) curves were plotted for these patients to assess the accuracy of the prognostic model. Using immunohistochemistry the protein levels of the genes associated with risk were assessed.ResultsWe determined 37 ARGs were differentially expressed between endometrial cancer and healthy tissues. These genes were enriched in the biological processes and signaling pathways related to autophagy. Four ARGs (CDKN2A, PTK6, ERBB2 and BIRC5) were selected to establish a prognostic model of endometrial cancer. Kaplan–Meier survival analysis suggested that high-risk groups have significantly shorter survival times than low-risk groups. The area under the ROC curve indicated that the prognostic model for survival prediction was relatively accurate. Immunohistochemistry suggested that among the four ARGs the protein levels of CDKN2A, PTK6, ERBB2, and BIRC5 were higher in endometrial cancer than healthy endometrial tissue.ConclusionsOur prognostic model assessing four ARGs (CDKN2A, PTK6, ERBB2, and BIRC5) suggested their potential as independent predictive biomarkers and therapeutic targets for endometrial cancer.
Highlights
Endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing
The results showed these autophagy related genes (ARGs) were primarily involved with the intrinsic apoptotic signaling pathway, processes utilizing the autophagic mechanism, the cellular response to oxidative stress, integral components of the mitochondrial outer membrane, autophagosome membrane, protease binding, and heat shock protein binding (Fig. 2a, b)
area under the curve (AUC) curves of other risk factors were plotted to compare the prognostic value of different criteria, and the results showed that our prognostic model was better than traditional prognostic indicators in predicting the survival of patients with endometrial cancer, including clinical grade, age, etc. (Supplemental Fig. S2)
Summary
Endometrial cancer is the fourth most common malignant tumor in women and the number of women being diagnosed is increasing. Many studies have attempted to clarify the role and complex functionalities of autophagy in malignant tumors with the intent of suppressing the development of malignancies by upregulating or inhibiting autophagy [11]. Endometrial cancer is one of the most common malignant tumors in women. It ranks fourth among the European and North American women, accounting for approximately 6% of new cancer cases and 3% of cancer deaths every year; most of the incidences occur during the perimenopausal and menopausal periods [12]. Recurrence and metastasis occur in some patients, for whom radiotherapy, chemotherapy, or a combination both is required; outcomes are poor [13,14,15,16]
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