Abstract
BackgroundTumor biomechanics correlates with the progression and prognosis of endometrial carcinoma (EC). The objective of this study is to construct a risk model using the mechanical stimulus-related genes in EC.MethodsWe retrieved the transcriptome profiling and clinical data of EC from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB). Differentially expressed mechanical stimulus-related genes were extracted from the databases, and then the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a risk model. A nomogram integrating the genes and the clinicopathological characteristics was established and validated using the Kaplan-Meier survival and receiver operating characteristic (ROC) curves to estimate the overall survival (OS) of EC patients. Protein profiling technology and immunofluorescence technique were performed to verify the connection between biomechanics and EC.ResultsIn total, 79 mechanical stimulus-related genes were identified by analyzing the two databases. Based on the LASSO regression analysis, 7 genes were selected for the establishment of the risk model. This model showed a good performance in terms of the prognostic accuracy in high- and low-risk groups. The area under the ROC curves (AUC) of this model was 0.697, 0.712 and 0.723 for 3-, 5- and 7-year OS, respectively. Then, a nomogram integrating the genes of the risk model and clinical features was constructed. The nomogram could accurately predict the OS (AUC = 0.779, 0.812 and 0.806 for 3-, 5- and 7-year OS, respectively). The results of the protein profiling technology and immunofluorescence revealed the expression of cytoskeleton proteins to be correlated with the Matrigel stiffness degree.ConclusionsIn summary, a risk model of 7 mechanical stimulus-related genes was identified in EC. A nomogram based on this risk model and combining the clinicopathological features to assess the overall survival of EC showed high practical value.
Highlights
Endometrial cancer (EC) represents one of the most common gynecologic malignancies in China and around the world with an increasing incidence [1]
We identified a set of EC genes that are related to the mechanical stimulus according to The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB)
GO analysis was carried out to elucidate the potential function of these 79 overlapping genes. These differentially expressed genes (DEGs) were mostly significantly enriched in the biological process (BP) term of “response to mechanical stimulus” (P-value < 0.05), in addition to the cellular component (CC) term of “cellular response to external stimulus” and molecular function (MF) term of “cellular response to abiotic stimulus. These results indicated that these DEGs were distributed in the mechanical stimulus-related processes and pathways, which have been proved to play a pivotal role in the tumorigenesis and progression of malignant tumors
Summary
Endometrial cancer (EC) represents one of the most common gynecologic malignancies in China and around the world with an increasing incidence [1]. Due to the unclear pathogenesis and molecular mechanism, the prognosis and management of EC are complicated. There is a need to explore the molecular mechanism of EC and detect the novel factors related to its diagnosis and prognosis. Malignant cells undergo cell mechanics and particular biomechanical properties in their growth, invasion and extravasation [3]. Biomechanics play a key role in the pathogenesis, diagnosis and prognosis of malignant tumors. Current studies focus more on the cellular mechanism, while the clinical level is rarely involved. Tumor biomechanics correlates with the progression and prognosis of endometrial carcinoma (EC).
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