The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

Yu, Zuwei; Feng, Shao-Ting; Zhang, Di; Cao, Xuchen; Yu, Yue; Wang, Xin

doi:10.1186/s12935-021-02090-9

Cited by 16 publications

(12 citation statements)

References 37 publications

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“…Moreover, age and risk scores were significantly associated with survival probability. This is consistent with the findings of previous studies ( 50 ).…”

Section: Discussionsupporting

confidence: 94%

The role of lactate metabolism-related LncRNAs in the prognosis, mutation, and tumor microenvironment of papillary thyroid cancer

Xia

Wang

et al. 2023

Front. Endocrinol.

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BackgroundLactate, a byproduct of glucose metabolism, is primarily utilized for gluconeogenesis and numerous cellular and organismal life processes. Interestingly, many studies have demonstrated a correlation between lactate metabolism and tumor development. However, the relationship between long non-coding RNAs (lncRNAs) and lactate metabolism in papillary thyroid cancer (PTC) remains to be explored.MethodsLactate metabolism-related lncRNAs (LRLs) were obtained by differential expression and correlation analyses, and the risk model was further constructed by least absolute shrinkage and selection operator analysis (Lasso) and Cox analysis. Clinical, immune, tumor mutation, and enrichment analyses were performed based on the risk model. The expression level of six LRLs was tested using RT-PCR.ResultsThis study found several lncRNAs linked to lactate metabolism in both The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Using Cox regression analysis, 303 lactate LRLs were found to be substantially associated with prognosis. Lasso was done on the TCGA cohort. Six LRLs were identified as independent predictive indicators for the development of a PTC prognostic risk model. The cohort was separated into two groups based on the median risk score (0.39717 -0.39771). Subsequently, Kaplan-Meier survival analysis and multivariate Cox regression analysis revealed that the high-risk group had a lower survival probability and that the risk score was an independent predictive factor of prognosis. In addition, a nomogram that can easily predict the 1-, 3-, and 5-year survival rates of PTC patients was established. Furthermore, the association between PTC prognostic factors and tumor microenvironment (TME), immune escape, as well as tumor somatic mutation status was investigated in high- and low-risk groups. Lastly, gene expression analysis was used to confirm the differential expression levels of the six LRLs.ConclusionIn conclusion, we have constructed a prognostic model that can predict the prognosis, mutation status, and TME of PTC patients. The model may have great clinical significance in the comprehensive evaluation of PTC patients.

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“…Moreover, age and risk scores were significantly associated with survival probability. This is consistent with the findings of previous studies ( 50 ).…”

Section: Discussionsupporting

confidence: 94%

The role of lactate metabolism-related LncRNAs in the prognosis, mutation, and tumor microenvironment of papillary thyroid cancer

Xia

Wang

et al. 2023

Front. Endocrinol.

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“…In order to explore the impact of multiple clinical traits and risk score on the prognosis of patients, we further performed a multivariate Cox analysis, which showed that age and risk score were indeed independent risk factors for the prognosis of thyroid cancer patients. The risk score, as an independent risk factor for prognosis, has also been studied in other diseases ( 40 ).In conclusion, this risk model has higher diagnostic power than previous cluster analyses and is more helpful in assessing patient prognosis.…”

Section: Discussionmentioning

confidence: 98%

“…A study on breast cancer showed that KIAA1429 can be a carcinogenic factor of breast cancer by regulating CDK1 independently of m6A ( 56 ). RBM15 is an important factor in X chromosome silencing and is expressed in breast tissue ( 40 , 57 – 59 ). Studies have also shown that estrogen can independently increase the expression of the RBM15 gene and is associated with the occurrence of breast diseases ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

“…To further understand the function of m6A-related genes in thyroid cancer, we selected 17 m6A-related genes ( 40 – 42 ) for clinical correlation analysis, immune infiltration analysis and immunotherapy analysis. In this study, thyroid cancer patients were divided into 2 clusters using consensus clustering based on the expression of 17 m6A-related genes.…”

Section: Introductionmentioning

confidence: 99%

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Effect of the m6ARNA gene on the prognosis of thyroid cancer, immune infiltration, and promising immunotherapy

Xia

Wang²,

Ye³

et al. 2022

Front. Immunol.

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BackgroundAccumulating evidence suggests that N6-methyladenosine (m6A) RNA methylation plays an important role in tumor proliferation and growth. However, its effect on the clinical prognosis, immune infiltration, and immunotherapy response of thyroid cancer patients has not been investigated in detail.MethodsClinical data and RNA expression profiles of thyroid cancer were extracted from the Cancer Genome Atlas-thyroid carcinoma (TCGA-THCA) and preprocessed for consensus clustering. The risk model was constructed based on differentially expressed genes (DEGs) using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. The associations between risk score and clinical traits, immune infiltration, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), immune infiltration, and immunotherapy were assessed. Immunohistochemistry was used to substantiate the clinical traits of our samples.ResultsGene expression analysis showed that 17 genes, except YHTDF2, had significant differences (vs healthy control, P<0.001). Consensus clustering yielded 2 clusters according to their clinical features and estimated a poorer prognosis for Cluster 1 (P=0.03). The heatmap between the 2 clusters showed differences in T (P<0.01), N (P<0.001) and stage (P<0.01). Based on univariate Cox and LASSO regression, a risk model consisting of three high-risk genes (KIAA1429, RBM15, FTO) was established, and the expression difference between normal and tumor tissues of three genes was confirmed by immunohistochemical results of our clinical tissues. KEGG and GSEA analyses showed that the risk DEGs were related mainly to proteolysis, immune response, and cancer pathways. The levels of immune infiltration in the high- and low-risk groups were different mainly in iDCs (P<0.05), NK cells (P<0.05), and type-INF-II (P<0.001). Immunotherapy analysis yielded 30 drugs associated with the expression of each gene and 20 drugs associated with the risk score.ConclusionsOur risk model can act as an independent marker for thyroid cancer and provides promising immunotherapy targets for its treatment.

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“…We found m6A potential regulatory sites in these three genes in the RNA epigenetic database ( 26 ). In 450 patients with PTC, most of the m6A RNA modification regulators were found to be downregulated, and a risk model was constructed based on 3 m6A RNA modification regulator genes ( FTO , RBM15 , and KIAA1429 ) that may be used as an independent predictive biomarker in PTC ( 44 ). These results suggest that the high expression of these 3 DEGs in tumor may be related to DNA methylation, mRNA methylation modification and potential transcription factor regulation.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Revealed a 3-Gene Panel Predicted the Diagnosis and Prognosis of Thyroid Papillary Carcinoma and Associated With Tumor Immune Microenvironment

Chen

Wang

et al. 2022

Front. Oncol.

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ObjectiveThe objective of this research was to screen prognostic related genes of thyroid papillary carcinoma (PTC) by single-cell RNA sequencing (scRNA-seq), to construct the diagnostic and prognostic models based on The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) data, and to evaluate the association between tumor immune microenvironment and the prognostic model.MethodThe differentially expressed genes (DEGs) and tumor evolution were analyzed by scRNA-seq based on public databases. The potential regulatory networks of DEGs related to prognosis were analyzed by multi-omics data in the THCA. Logistic regression and Cox proportional hazards regression were utilized to construct the diagnosis and prognostic model of PTC. The performance of the diagnostic model was verified by bulk RNA sequencing (RNA-seq) of our cohort. The tumor immune microenvironment associated with the prognostic model was evaluated using multi-omics data. In addition, qRT-PCR was performed on tumor tissues and adjacent normal tissues of 20 patients to verify the expression levels of DEGs.ResultsThe DEGs screened by scRNA-seq can distinguish between tumor and healthy samples. DEGs play different roles in the evolution from normal epithelial cells to malignant cells. Three DEGs ((FN1, CLU, and ANXA1)) related to prognosis were filtered, which may be regulated by DNA methylation, RNA methylation (m6A) and upstream transcription factors. The area under curve (AUC) of the diagnostic model based on 3-gene in the validation of our RNA-seq was 1. In the prognostic model based on 3-gene, the overall survival (OS) of high-risk patients was shorter. Combined with the clinical information of patients, a nomogram was constructed by using tumor size (pT) and risk score to quantify the prognostic risk. The age and tumor size of high-risk patients in the prognostic model were greater. In addition, the increase of tumor mutation burden (TMB) and diversity of T cell receptor (TCR), and the decrease of CD8+ T cells in high-risk group suggest the existence of immunosuppressive microenvironment.ConclusionWe applied the scRNA-seq pipeline to focus on epithelial cells in PTC, simulated the process of tumor evolution, and revealed a prognostic prediction model based on 3 genes, which is related to tumor immune microenvironment.

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The functions and prognostic values of m6A RNA methylation regulators in thyroid carcinoma

Cited by 16 publications

References 37 publications

The role of lactate metabolism-related LncRNAs in the prognosis, mutation, and tumor microenvironment of papillary thyroid cancer

The role of lactate metabolism-related LncRNAs in the prognosis, mutation, and tumor microenvironment of papillary thyroid cancer

Effect of the m6ARNA gene on the prognosis of thyroid cancer, immune infiltration, and promising immunotherapy

Single-Cell RNA Sequencing Revealed a 3-Gene Panel Predicted the Diagnosis and Prognosis of Thyroid Papillary Carcinoma and Associated With Tumor Immune Microenvironment

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