scholarly journals A novel epithelial-mesenchymal transition-related gene signature for prognosis prediction in patients with lung adenocarcinoma

Heliyon ◽  
2022 ◽  
pp. e08713
Author(s):  
Shengyu Feng ◽  
Ce Huang ◽  
Liuling Guo ◽  
Hao Wang ◽  
Hailiang Liu
2017 ◽  
Vol 3 (3) ◽  
pp. 57 ◽  
Author(s):  
Borong Shao ◽  
Carlo Vittorio Cannistraci ◽  
Tim OF. Conrad

Epithelial mesenchymal transition (EMT) process has been shown as highly relevant to cancer prognosis. However, although different biological network-based biomarker identification methods have been proposed to predict cancer prognosis, EMT network has not been directly used for this purpose. In this study, we constructed an EMT regulatory network consisting of 87 molecules and tried to select features that are useful for prognosis prediction in Lung Adenocarcinoma (LUAD). To incorporate multiple molecular profiles, we obtained four types of molecular data including mRNA-Seq, copy number alteration (CNA), DNA methylation, and miRNA-Seq data from The Cancer Genome Atlas. The data were mapped to the EMT network in three alternative ways: mRNA-Seq and miRNA-Seq, DNA methylation, and CNA and miRNA-Seq. Each mapping was employed to extract five different sets of features using discretization and network-based biomarker identification methods. Each feature set was then used to predict prognosis with SVM and logistic regression classifiers. We measured the prediction accuracy with AUC and AUPR values using 10 times 10-fold cross validation. For a more comprehensive evaluation, we also measured the prediction accuracies of clinical features, EMT plus clinical features, randomly picked 87 molecules from each data mapping, and using all molecules from each data type. Counter-intuitively, EMT features do not always outperform randomly selected features and the prediction accuracies of the five feature sets are mostly not significantly different. Clinical features are shown to give the highest prediction accuracies. In addition, the prediction accuracies of both EMT features and random features are comparable as using all features (more than 17,000) from each data type.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gongmin Zhu ◽  
Hongwei Xia ◽  
Qiulin Tang ◽  
Feng Bi

Abstract Background Tumor metastasis is one of the leading reasons of the dismal prognosis of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is closely associated with tumor metastasis including HCC. The purpose of this study is to construct and validate an EMT-related gene signature for predicting the prognosis of HCC patients. Methods Gene expression data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to found the EMT-related gene sets which were obviously distinct between normal samples and paired HCC samples. Cox regression analysis was used to develop an EMT-related prognostic signature, and the performance of the signature was evaluated by Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. A nomogram incorporating the independent predictors was established. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the hub genes in HCC cell lines, and the role of PDCD6 in the metastasis of HCC was determined by functional experiments. Results An EMT-related 5-gene signature (PDCD6, TCOF1, TRIM28, EZH2 and FAM83D) was constructed using univariate and multivariate Cox regression analysis. Based on the signature, the HCC patients were classified into high- and low-risk groups, and patients in high-risk group had a poor prognosis. Time-dependent ROC and Cox regression analyses suggested that the signature could predict HCC prognosis exactly and independently. The predictive capacity of the signature was also validated in two external cohorts. GSEA results showed that many cancer-related signaling pathways such as PI3K/Akt/mTOR pathway and TGF-β/SMAD pathway were enriched in high-risk group. The result of qRT-PCR revealed that PDCD6, TCOF1 and FAM83D were highly expressed in HCC cancer cells. Among them, PDCD6 were found to promote cell migration and invasion. Conclusion The EMT-related 5-gene signature can serve as a promising prognostic biomarker for HCC patients and may provide a novel mechanism of HCC metastasis.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zizhen Zhang ◽  
Sheng Zheng ◽  
Yifeng Lin ◽  
Jiawei Sun ◽  
Ning Ding ◽  
...  

Abstract Background The epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing. EMT also plays an important role in cancer invasion, metastasis, and chemoresistance. Additionally, EMT is partially responsible for chemoresistance in colorectal cancer (CRC). The aim of this research is to develop an EMT-based prognostic signature in CRC. Methods RNA-seq and microarray data, together with clinical information, were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. A total of 244 differentially expressed EMT-related genes (ERGs) were obtained by comparing the expression between normal and tumor tissues. An EMT-related signature of 11 genes was identified as crucially related to the overall survival (OS) of patients through univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO), and Cox regression analysis. Finally, we established a clinical nomogram to predict the survival possibility of CRC patients by integrating clinical characteristics and the EMT-related gene signature. Results Two hundred and forty-four differentially expressed ERGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that EMT-related signaling pathway genes were highly related to CRC. Kaplan-Meier analysis revealed that the 11-EMT signature could significantly distinguish high- and low-risk patients in both TCGA and GEO CRC cohorts. In addition, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusion We developed a novel EMT-related gene signature for the prognosis prediction of CRC patients, which could improve the individualized outcome prediction in CRC.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yuxuan Wang ◽  
Weikang Chen ◽  
Minqi Zhu ◽  
Lei Xian

Background: Lung adenocarcinoma (LUAD) is a malignant tumor with high heterogeneity and poor prognosis. Ferroptosis, a form of regulated cell-death–related iron, has been proven to trigger inflammation-associated immunosuppression in the tumor microenvironment, which promotes tumor growth. Therefore, the clinical prognostic value of ferroptosis-related genes in LUAD needs to be further explored.Method: In this study, we downloaded the mRNA expression profiles and corresponding clinical data of LUAD patients from the Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct ferroptosis-related gene signature. Based on these, we established the nomograms for prognosis prediction and validated the model in the GSE72094 dataset. The cell type was identified using the CIBERSORT algorithm for estimating relative subsets of RNA transcripts, which was then used to screen significant tumor immune-infiltrating cells associated with the LUAD prognosis prediction model. Subsequently, we applied co-expression analysis to reveal the relationship between ferroptosis-related genes and significant immune cells.Results: The univariate COX regression analysis showed that 20 genes were associated with the overall survival (OS) as prognostic differentially expressed genes (DEGs) (FDR <0.05). Patients were divided into two risk groups using a 13-gene signature, with the high-risk group having a significantly worse OS than their low-risk counterparts (p < 0.001). We used receiver operating characteristic (ROC) curve analysis to confirm the predictive capacity of the signature. Besides, we identified seven pairs of ferroptosis-related genes and tumor-infiltrating immune cells associated with the prognosis of LUAD patients.Conclusion: In this study, we construct a ferroptosis-related gene signature that can be used for prognostic prediction in LUAD. In addition, we reveal a potential connection between ferroptosis and tumor-infiltrating immune cells.


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoli Liu ◽  
Zuwei Yin ◽  
Linping Xu ◽  
Huaimin Liu ◽  
Lifeng Jiang ◽  
...  

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.


2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110148
Author(s):  
Xue Qiao ◽  
Xing Niu ◽  
Jiayi Liu ◽  
Lijie Chen ◽  
Yan Guo ◽  
...  

Ameloblastoma is a common odontogenic epithelial tumor that exhibits various biological behaviors, ranging from simple cystic expansion to aggressive solid masses characterized by local invasiveness, a high risk of recurrence, and even malignant transformation. We report on two cases of unusually large solid ameloblastomas. We detected epithelial–mesenchymal transition-related gene expression and HRAS gene single nucleotide polymorphisms, providing possible molecular evidence of mesenchymal morphological changes in ameloblastoma. The detailed analysis of the pathogenesis of these two cases of ameloblastoma may deepen our understanding of this rare disease and offer promising targets for future targeted therapy.


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