Estimating the prognosis of esophageal squamous cell carcinoma based on The Cancer Genome Atlas (TCGA) of m6A methylation-associated genes

Pan, Yu; Lu, Xianfeng; Yang, Xueqin; Yang, Yi; Wang, Dong; Li, Mengxia; Guan, Wei; Xu, Mingfang

doi:10.21037/jgo-21-686

Cited by 11 publications

(7 citation statements)

References 43 publications

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“…Therefore, it is necessary to identify novel biomarkers that could be effective therapeutic targets in EC patients. Previous studies ( 33 , 34 ) reported that a signature on the basis of m6A-associated gene expressions had good prediction ability for EC patients. However, there is still no m6A-associated lncRNA prognostic risk model that predicts the prognoses of EC patients.…”

Section: Discussionmentioning

confidence: 88%

Prognostic model based on m6A-associated lncRNAs in esophageal cancer

Wang

Dong

et al. 2022

Front. Endocrinol.

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BackgroundThis research aimed to build an m6A-associated lncRNA prognostic model of esophageal cancer that can be used to predict outcome in esophageal cancer patients.MethodsRNA sequencing transcriptome data and clinical information about patients with esophageal cancer were obtained according to TCGA. Twenty-four m6A-associated genes were selected based on previous studies. m6A-associated lncRNAs were determined through Pearson correlation analysis. Three m6A-associated lncRNA prognostic signatures were built through analysis of the training set using univariate, LASSO, and multivariate Cox regression. To validate the stabilization of the risk signature, Kaplan–Meier and ROC curve analyses were performed on the testing and complete sets. The prognoses of EC patients were predicted quantitatively by building a nomogram. GSEA was conducted to analyze the underlying signaling pathways and biological processes. To identify the underlying mechanisms through which the lncRNAs act, we constructed a PPI network and a ceRNA network and conducted GO and KEGG pathway analyses. EC samples were evaluated using the ESTIMATE algorithm to compute stromal, immune, and estimate scores. The ssGSEA algorithm was used to quantitatively infer immune cell infiltration and immune functions. The TIDE algorithm was performed to simulate immune evasion and predict the response to immunotherapy.ResultsWe identified and validated an m6A-associated lncRNA risk model in EC that could correctly and reliably predict the OS of EC patients. The ceRNA network, PPI network, and GO and KEGG pathway analyses confirmed and the underlying mechanisms and functions provided enlightenment regarding therapeutic strategies for EC. Immunotherapy responses were better in the low-risk subgroup, and PD-1 and CTLA4 checkpoint immunotherapy benefited the patients in the low-risk subgroup.ConclusionsWe constructed a new m6A-related lncRNA prognostic risk model of EC, based on three m6A-related lncRNAs: LINC01612, AC025166.1 and AC016876.2, that can predict the prognoses of EC patients.

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Section: Discussionmentioning

confidence: 88%

Prognostic model based on m6A-associated lncRNAs in esophageal cancer

Wang

Dong

et al. 2022

Front. Endocrinol.

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“…In hepatocellular carcinoma, ALKBH5 promoted macrophage recruitment through upregulating MAP3K8 expression in an m 6 A-dependent manner [ 174 ]. In ESCA, some studies revealed that the expression of m 6 A regulators was associated with PD-L1 expression and immune cells infiltration, suggesting the role of m 6 A regulators as an immune therapy target individually or in combination with ICIs [ 128 , 155 , 156 , 177 ]. However, how m 6 A regulators affect the TIME of ESCA has not been reported, which provides a direction for future research in ESCA.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, further studies are needed to comprehensively analyze the relation between the expression of m 6 A regulators and the survival of ESCA patients due to the complexity of the m 6 A regulatory network. Based on information from the public database, some researchers constructed a prognostic signature according to the expression of m 6 A regulators to predict the survival of ESCA patients [ 79 , 84 , 130 , 136 , 155 , 156 ]. For example, Xu et al [ 130 ] analyzed the RNA sequencing transcriptome data of 13 m 6 A regulators from the TCGA ESCA database, constructed a prognostic signature, which consisted of HNRNPC and ALKBH5, and established a formula to calculate the risk score.…”

Section: The Role Of M 6 a Regulators In Developme...mentioning

confidence: 99%

The Role of m6A Modification and m6A Regulators in Esophageal Cancer

Niu

Wang

et al. 2022

Cancers

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N6-methyladenosine (m6A) modification, the most prevalent RNA modification, is involved in all aspects of RNA metabolism, including RNA processing, nuclear export, stability, translation and degradation. Therefore, m6A modification can participate in various physiological functions, such as tissue development, heat shock response, DNA damage response, circadian clock control and even in carcinogenesis through regulating the expression or structure of the gene. The deposition, removal and recognition of m6A are carried out by methyltransferases, demethylases and m6A RNA binding proteins, respectively. Aberrant m6A modification and the dysregulation of m6A regulators play critical roles in the occurrence and development of various cancers. The pathogenesis of esophageal cancer (ESCA) remains unclear and the five-year survival rate of advanced ESCA patients is still dismal. Here, we systematically reviewed the recent studies of m6A modification and m6A regulators in ESCA and comprehensively analyzed the role and possible mechanism of m6A modification and m6A regulators in the occurrence, progression, remedy and prognosis of ESCA. Defining the effect of m6A modification and m6A regulators in ESCA might be helpful for determining the pathogenesis of ESCA and providing some ideas for an early diagnosis, individualized treatment and improved prognosis of ESCA patients.

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“…Furthermore, some studies have shown that YTHDF3 contributes to the formation of the tumor microenvironment and could be used as an immune-related marker. High YTHDF3 expression indicates poor survival with a diversity of lymphocyte infiltration in breast cancer, as well as esophageal squamous cell carcinoma and head and neck squamous cell carcinoma ( Zhang et al, 2021 ; Zhao et al, 2021 ; Pu et al, 2022 ). The above research shows that YTHDF3 may be a potential therapeutic target related to tumor-infiltrating immune cells.…”

Section: Ythdfs and Tumor Immune Responsesmentioning

confidence: 99%

YT521-B homology domain family proteins as N6-methyladenosine readers in tumors

et al. 2022

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N6-methyladenosine (m6A) is the most abundant internal chemical modification of eukaryotic mRNA and plays diverse roles in gene regulation. The m6A modification plays a significant role in numerous cancer types, including kidney, stomach, lung, bladder tumors, and melanoma, through varied mechanisms. As direct m6A readers, the YT521-B homology domain family proteins (YTHDFs) play a key role in tumor transcription, translation, protein synthesis, tumor stemness, epithelial–mesenchymal transition (EMT), immune escape, and chemotherapy resistance. An in-depth understanding of the molecular mechanism of YTHDFs is expected to provide new strategies for tumor treatment. In this review, we provide a systematic description of YTHDF protein structure and its function in tumor progression.

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Estimating the prognosis of esophageal squamous cell carcinoma based on The Cancer Genome Atlas (TCGA) of m6A methylation-associated genes

Cited by 11 publications

References 43 publications

Prognostic model based on m6A-associated lncRNAs in esophageal cancer

Prognostic model based on m6A-associated lncRNAs in esophageal cancer

The Role of m6A Modification and m6A Regulators in Esophageal Cancer

YT521-B homology domain family proteins as N6-methyladenosine readers in tumors

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