Dataset Information

A novel prognostic model for papillary thyroid cancer based on epithelial-mesenchymal transition-related genes.

ABSTRACT:

Background

The frequent incidence of postsurgical recurrence issues in papillary thyroid cancer (PTC) patients is a primary concern considering the low cancer-related mortality. Previous studies have demonstrated that epithelial-mesenchymal transition (EMT) activation is closely related to PTC progression and invasion. In this study, we aimed to develop a novel EMT signature and ancillary nomogram to improve personalized prediction of progression-free interval (PFI).

Methods

First, we carried out a differential analysis of PTC samples and pairwise normal thyroid samples to explore the differentially expressed genes (DEGs). The intersection of the DEGs with EMT-related genes (ERGs) were identified as differentially expressed EMT-related genes (DE-ERGs). We determined PFI-related DE-ERGs by Cox regression analysis and then established a novel gene classifier by LASSO regression analysis. We validated the signature in external datasets and in multiple cell lines. Further, we used uni- and multivariate analyses to identify independent prognostic characters.

Results

We identified 244 prognosis-related DE-ERGs. The 244 DE-ERGs were associated with several pivotal oncogenic processes. We also constructed a novel 10-gene signature and relevant prognostic model for recurrence prediction of PTC. The 10-gene signature had a C-index of 0.723 and the relevant nomogram had a C-index of 0.776. The efficacy of the signature and nomogram was satisfying and closely correlated with relevant clinical parameters. Furthermore, the signature also had a unique potential in differentiating anaplastic thyroid cancer (ATC) samples.

Conclusions

The novel EMT signature and nomogram are useful and convenient for personalized management for thyroid cancer.

SUBMITTER: Liu R

PROVIDER: S-EPMC9741981 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

A novel prognostic model for papillary thyroid cancer based on epithelial-mesenchymal transition-related genes.

Liu Rui R Cao Zhen Z Pan Meng M Wu Mengwei M Li Xiaobin X Yuan Hongwei H Liu Ziwen Z

Cancer medicine 20220524 23

<h4>Background</h4>The frequent incidence of postsurgical recurrence issues in papillary thyroid cancer (PTC) patients is a primary concern considering the low cancer-related mortality. Previous studies have demonstrated that epithelial-mesenchymal transition (EMT) activation is closely related to PTC progression and invasion. In this study, we aimed to develop a novel EMT signature and ancillary nomogram to improve personalized prediction of progression-free interval (PFI).<h4>Methods</h4>First ...[more]

PMID: 35608185

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Project description:BackgroundsEpithelial-mesenchymal transition (EMT) is a sequential process where tumor cells develop from the epithelial state to the mesenchymal state. EMT contributes to various tumor functions including initiation, propagating potential, and resistance to therapy, thus affecting the survival time of patients. The aim of this research is to set up an EMT-related prognostic signature for endometrial cancer (EC).MethodsEMT-related gene (ERG) expression and clinical data were acquired from The Cancer Genome Atlas (TCGA). The entire set was randomly divided into two sets, one for contributing the risk model (risk score) and the other for validating. Univariate and multivariate Cox proportional hazards regression analyses were applied to the training set to select the prognostic ERGs. The expression of 10 ERGs was confirmed by qRT-PCR in clinical samples. Then, we developed a nomogram predicting 1-/3-/5-year survival possibility combining the risk score and clinical factors. The entire set was stratified into the high- and low-risk groups, which was used to analyze the immune infiltrating, tumorigenesis pathways, and response to drugs.ResultsA total of 220 genes were screened out from 1,316 ERGs for their differential expression in tumor versus normal. Next, 10 genes were found to be associated with overall survival (OS) in EC, and the expression was validated by qRT-PCR using clinical samples, so we constructed a 10-ERG-based risk score to distinguish high-/low-risk patients and a nomogram to predict survival rate. The calibration plots proved the predictive value of our model. Gene Set Enrichment Analysis (GSEA) discovered that in the low-risk group, immune-related pathways were enriched; in the high-risk group, tumorigenesis pathways were enriched. The low-risk group showed more immune activities, higher tumor mutational burden (TMB), and higher CTAL4/PD1 expression, which was in line with a better response to immune checkpoint inhibitors. Nevertheless, response to chemotherapeutic drugs turned out better in the high-risk group. The high-risk group had higher N 6-methyladenosine (m6A) RNA expression, microsatellite instability level, and stemness indices.ConclusionWe constructed the ERG-related signature model to predict the prognosis of EC patients. What is more, it might offer a reference for predicting individualized response to immune checkpoint inhibitors and chemotherapeutic drugs.

Dataset Information

A novel prognostic model for papillary thyroid cancer based on epithelial-mesenchymal transition-related genes.

Background

Methods

Results

Conclusions

Publications

A novel prognostic model for papillary thyroid cancer based on epithelial-mesenchymal transition-related genes.

Similar Datasets

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