M6A Regulatory Genes Play an Important Role in the Prognosis, Progression and Immune Microenvironment of Pancreatic Adenocarcinoma

Xu, Fangshi; Zhang, Zhengliang; Miao, Yuan; Zhao, Yidi; Zhou, Yang; Pei, Honghong; Bai, Linquan

doi:10.1080/07357907.2020.1834576

Cited by 34 publications

(40 citation statements)

References 53 publications

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“…It was reported that ZC3H13 may be a key upstream factor of nuclear factor-κB (NF-κB) that is responsible for NF-κB activation (Luo et al, 2009). Numerous studies have shown that the five candidate m6A regulators participate in the occurrence and development of tumors, including proliferation, invasion, radiotherapy resistance, and prognosis (Zalfa et al, 2017;Zhu et al, 2019;Chen et al, 2020;He et al, 2020;Xu et al, 2020). However, there are no reports on the relationship between the five candidate m6A regulators and childhood asthma.…”

Section: Discussionmentioning

confidence: 99%

Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database

et al. 2021

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RNA N6-methyladenosine (m6A) regulators play important roles in a variety of biological functions. Nonetheless, the roles of m6A regulators in childhood asthma remain unknown. In this study, 11 significant m6A regulators were selected using difference analysis between non-asthmatic and asthmatic patients from the Gene Expression Omnibus GSE40888 dataset. The random forest model was used to screen five candidate m6A regulators (fragile X mental retardation 1, KIAA1429, Wilm’s tumor 1-associated protein, YTH domain-containing 2, and zinc finger CCCH domain-containing protein 13) to predict the risk of childhood asthma. A nomogram model was established based on the five candidate m6A regulators. Decision curve analysis indicated that patients could benefit from the nomogram model. The consensus clustering method was performed to differentiate children with asthma into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. The patients in clusterB had higher m6A scores than those in clusterA. Furthermore, we found that the patients in clusterA were linked to helper T cell type 1 (Th1)-dominant immunity while those in clusterB were linked to Th2-dominant immunity. In summary, m6A regulators play nonnegligible roles in the occurrence of childhood asthma. Our investigation of m6A patterns may be able to guide future immunotherapy strategies for childhood asthma.

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Section: Discussionmentioning

confidence: 99%

Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database

et al. 2021

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“…M6A RNA methylation is the most common modification and has been proven to play an important role in tumor progression [ 38 ]. Correspondingly, the m6A regulatory genes were also found to be closely associated with AML [ 39 ], glioblastoma [ 19 ], liver cancer [ 40 ], breast cancer [ 41 ] and pancreatic cancer [ 20 ]. However, the crucial roles of m6A-related genes in ACC have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…In breast cancer (BRC), elevated METTL3 can promote tumor progression by inhibiting the tumor suppressor let-7g [ 18 ]. Although some research has explored the function of m6A regulatory genes in some cancers, such as renal cancer [ 19 ], pancreatic adenocarcinoma [ 20 ] and hepatocellular carcinoma [ 21 ], the role of that in ACC has not been fully elucidated. Therefore, we performed bioinformatic analyses for expression, prognostic value and immunological effect of m6A-related genes in ACC by using TCGA, GEO and GEPIA databases.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic analyses and experimental validation of the role of m6A RNA methylation regulators in progression and prognosis of adrenocortical carcinoma

Guan

et al. 2021

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M6A-related genes have been proven to play an important role in many cancers. However, the role of that in adrenocortical carcinoma (ACC) has not been fully elucidated. In the present study, 77 ACC samples from TCGA database were divided into localized ( n = 46) and metastatic ( n = 31) groups. Three differential expression genes (DEGs) and five prognostic m6A genes were screened out. M6A-related risk signature (RBM15 and HNRNPC) was constructed by the Lasso regression analysis. In TCGA cohort (training cohort), the risk signature was identified as an ACC-independent prognostic factor and can distinguish the prognostic difference of ACC patients with clinical stage I-II, T3-4 and N0 stages. A nomogram combining T stage and m6A risk score was constructed to predict the overall survival rate (OSR) of individual at 1,2,3 year. Meanwhile, its prognostic value was also confirmed in the validation cohort (GSE33371 dataset). The potential associations between m6A risk level and immune checkpoint inhibitors (ICIs) therapy were also investigated via the TISIDB online tool. High m6A risk not only can suppress immunotherapy-related biological processes, but also repress the expressions of immune-checkpoint markers. Moreover, five pairs of clinical specimens were collected to confirm the overexpression of HNRNPC and non-ectopic expression of RBM15 in tumor tissues. HNRNPC was proven to promote the proliferation, migration and invasion of H295R and SW13 cells through MTT and Transwell assays. In conclusion, the m6A-related risk signature was beneficial for prognostic analysis and can affect immune microenvironment in ACC. HNRNPC played a pro-cancer role in ACC progression.

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“…For instance, the research by Li et al (2021) identified and verified a specific glycolysis-related prognostic model for patients with PAAD (risk score=0.1755 * KIF20A −0.1400 * CHST2 +0.0214 * MET). Moreover, Xu et al (2021) constructed and validated a novel prognostic signature for patients with PAAD based on the expression of N6-methyladenosine (m6A) regulator genes (Risk score=0.233 * KIAA1429 −0.087 * METTL3 −0.132 * METTL14 −0.035 * YTHDF1 −0.0286 * ALKBH5). However, most researchers have failed to focus on the considerable interconnection between genes when constructing prognostic signatures, and thus, the weighted gene co-expression network analysis (WGCNA) was developed.…”

Section: Introductionmentioning

confidence: 99%

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

et al. 2021

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Background: Pancreatic adenocarcinoma (PAAD) has a considerably bad prognosis, and its pathophysiologic mechanism remains unclear. Thus, we aimed to identify real hub genes to better explore the pathophysiology of PAAD and construct a prognostic panel to better predict the prognosis of PAAD using the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithms.Methods: WGCNA identified the modules most closely related to the PAAD stage and grade based on the Gene Expression Omnibus. The module genes significantly associated with PAAD progression and prognosis were considered as the real hub genes. Eligible genes in the most significant module were selected for construction and validation of a multigene prognostic signature based on the LASSO-Cox regression analysis in The Cancer Genome Atlas and the International Cancer Genome Consortium databases, respectively.Results: The brown module identified by WGCNA was most closely associated with the clinical characteristics of PAAD. Scaffold attachment factor B (SAFB) was significantly associated with PAAD progression and prognosis, and was identified as the real hub gene of PAAD. Moreover, both transcriptional and translational levels of SAFB were significantly lower in PAAD tissues compared with normal pancreatic tissues. In addition, a novel multigene-independent prognostic signature consisting of SAFB, SP1, and SERTAD3 was identified and verified. The predictive accuracy of our signature was superior to that of previous studies, especially for predicting 3- and 5-year survival probabilities. Furthermore, a prognostic nomogram based on independent prognostic variables was developed and validated using calibration curves. The predictive ability of this nomogram was also superior to the well-established AJCC stage and histological grade. The potential mechanisms of different prognoses between the high- and low-risk subgroups were also investigated using functional enrichment analysis, GSEA, ssGSEA, immune checkpoint analysis, and mutation profile analysis.Conclusion: SAFB was identified as the real hub gene of PAAD. A novel multigene-independent prognostic signature was successfully identified and validated to better predict PAAD prognosis. An accurate nomogram was also developed and verified to aid in the accurate treatment of tumors, as well as in early intervention.

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M6A Regulatory Genes Play an Important Role in the Prognosis, Progression and Immune Microenvironment of Pancreatic Adenocarcinoma

Cited by 34 publications

References 53 publications

Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database

Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database

Bioinformatic analyses and experimental validation of the role of m6A RNA methylation regulators in progression and prognosis of adrenocortical carcinoma

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

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