Abstract
BackgroundAutophagy is associated with cancer development. Autophagy-related genes play significant roles in endometrial cancer (EC), a major gynecological malignancy worldwide, but little was known about their value as prognostic markers. Here we evaluated the value of a prognostic signature based on autophagy-related genes for EC.MethodsFirst, various autophagy-related genes were obtained via the Human Autophagy Database and their expression profiles were downloaded from The Cancer Genome Atlas. Second, key prognostic autophagy-related genes were identified via univariate, LASSO and multivariate Cox regression analyses. Finally, a risk score to predict the prognosis of EC was calculated and validated by using the test and the entire data sets. Besides, the key genes mRNA expression were validated using quantitative real-time PCR in clinical tissue samples.ResultsA total of 40 differentially expressed autophagy-related genes in EC were screened and five of them were prognosis-related (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1). A prognostic signature was constructed based on these five genes using the train set, which stratified EC patients into high-risk and low-risk groups (p < 0.05). In terms of overall survival, the analyses of the test set and the entire set yielded consistent results (test set: p < 0.05; entire set: p < 0.05). Time-dependent ROC analysis suggested that the risk score predicted EC prognosis accurately and independently (0.674 at 1 year, 0.712 at 3 years and 0.659 at 5 years). A nomogram with clinical utility was built. Patients in the high-risk group displayed distinct mutation signatures compared with those in the low-risk group. For clinical sample validation, we found that EIF4EBP1and ERBB2 had higher level in EC than that in normal tissues while CDKN1B, DLC1 and GRID1 had lower level, which was consistent with the results predicted.ConclusionsBased on five autophagy-related genes (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1), our model can independently predict the OS of EC patients by combining molecular signature and clinical characteristics.
Highlights
We examined the relevance between autophagy-related genes (ARGs) expression profiles and clinical outcomes in 552 endometrial cancer (EC) patients from The Cancer Genome Atlas (TCGA)
Identification of differently expressed ARGs RNA sequencing (RNA-seq) and clinical data of 552 EC tissue samples and 23 non-tumor samples were downloaded from TCGA
Functional annotation of the differentially expressed ARGs According to the results of Enrichr database, in the aspect of biological processes, the genes were mostly enriched in apoptotic process, intrinsic apoptotic signaling pathway and intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Summary
Autophagy-related genes play significant roles in endometrial cancer (EC), a major gynecological malignancy worldwide, but little was known about their value as prognostic markers. We evaluated the value of a prognostic signature based on autophagy-related genes for EC. As an evolutionarily ancient and highly conserved biological behavior, autophagy plays a cytoprotective role in eukaryotic cells through degrading unnecessary or dysfunctional organelles under the condition of hypoxia, starvation, nutrition deficiency or high PH [1]. Wang et al Cancer Cell Int (2020) 20:306 the mechanisms of autophagy in cancer remain stagnantly understood. Endometrial cancer (EC) is one of the most common malignant diseases in women worldwide, with an estimated 61,880 newly-diagnosed cases and 12,160 deaths in the United States in 2019 [4]. To further improve the outcomes of EC treatments, physicians need to identify high-risk patients and tailor precise treatment
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