Characterization of m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration in Ovarian Cancer

Luo, Yihong; Sun, Xin; Xiong, Jian

doi:10.3389/fcell.2021.794801

Cited by 10 publications

(9 citation statements)

References 30 publications

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“…Whether this effect also exists in ovarian cancer, as well as other neoplasm of reproductive system, is worth further exploration. Also, Luo et al [56] found m6A affected the process of antigen presentation in the immune system and played an important role in TME cell infiltration in OC. Some m6A protein machineries and methylated gene loci have been found in OC, which may be used as therapeutic targets or prognostic markers in the future.…”

Section: Ovarian Cancermentioning

confidence: 99%

Role of m6A modification in female infertility and reproductive system diseases

Chen

Fang

et al. 2022

Int. J. Biol. Sci.

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Gamete abnormalities and reproductive system tumors have become a dominant cause of infertility, troubling people globally. In recent years, increasing evidence emerged and found that N6-methyladenosine (m6A) played a leading role in reproduction. The biological effects of m6A modification are dynamically and reversibly regulated by methyltransferases (writers), WTAP, METTL3, METTL14 and KIAA1429, demethylases (erasers), FTO and ALKBH5, and m6A binding proteins (readers), including YTH domain. In this review, we highlight the change of m6A modification in abnormal oogenesis, female reproductive system diseases including reproductive system tumors, adenomyosis, endometriosis, premature ovarian failure and polycystic ovary syndrome. Moreover, we review some of the mechanisms and the specific modified genes that have been identified. Especially, with the underlying mechanisms being uncovered, m6A and its protein machineries are expected to be the markers and targets for the diagnosis and treatment of female reproductive dysfunction.

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Section: Ovarian Cancermentioning

confidence: 99%

Role of m6A modification in female infertility and reproductive system diseases

Chen

Fang

et al. 2022

Int. J. Biol. Sci.

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“…In terms of ovarian OCs, a study demonstrated m1A modifications played critical roles in tumor immune microenvironment formation and prognosis of OC patients ( 51 ). Identically, m6A modification was proved to play an essential part in tumor microenvironment cell infiltration in OCs ( 52 ). This present study further analyzed the relationship of OC subtypes and immune types.…”

Section: Discussionmentioning

confidence: 99%

Ovarian cancer subtypes based on the regulatory genes of RNA modifications: Novel prediction model of prognosis

Zheng

Zhan

2022

Front. Endocrinol.

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BackgroundOvarian cancer (OC) is a female reproductive system tumor. RNA modifications play key roles in gene expression regulation. The growing evidence demonstrates that RNA methylation is critical for various biological functions, and that its dysregulation is related to the progression of cancer in human.MethodOC samples were classified into different subtypes (Clusters 1 and 2) based on various RNA-modification regulatory genes (RRGs) in the process of RNA modifications (m1A, m6A, m6Am, m5C, m7G, ac4C, m3C, and Ψ) by nonnegative matrix factorization method (NMF). Based on differently expressed RRGs (DERRGs) between clusters, a pathologically specific RNA-modification regulatory gene signature was constructed with Lasso regression. Kaplan-Meier analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic ability of the identified model. The correlations of clinicopathological features, immune subtypes, immune scores, immune cells, and tumor mutation burden (TMB) were also estimated between different NMF clusters and riskscore groups.ResultsIn this study, 59 RRGs in the process of RNA modifications (m1A, m6A, m6Am, m5C, m7G, ac4C, m3C, and Ψ) were obtained from TCGA database. These RRGs were interactional, and sample clusters based on these regulators were significantly correlated with survival rate, clinical characteristics (involving survival status and pathologic stage), drug sensibility, and immune microenvironment. Furthermore, Lasso regression based on these 21 DERRGs between clusters 1 and 2 constructed a four-DERRG signature (ALYREF, ZC3H13, WTAP, and METTL1). Based on this signature, 307 OC patients were classified into high- and low-risk groups based on median value of riskscores from lasso regression. This identified signature was significantly associated with overall survival, radiation therapy, age, clinical stage, cancer status, and immune cells (involving CD4+ memory resting T cells, plasma cells, and Macrophages M1) of ovarian cancer patients. Further, GSEA revealed that multiple biological behaviors were significantly enriched in different groups.ConclusionsOC patients were classified into two subtypes per these RRGs. This study identified four-DERRG signature (ALYREF, ZC3H13, WTAP, and METTL1) in OC, which was an independent prognostic model for patient stratification, prognostic evaluation, and prediction of response to immunotherapy in ovarian cancer by classifying OC patients into high- and low-risk groups.

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“…32 To depict the CNV landscape of the 21 m6A regulators across 23 chromosome pairs, we used the “RCircos” R package for visualization. 33,34…”

Section: Methodsmentioning

confidence: 99%

“…For evaluating prognosis, the Univariate Cox regression model was applied to each m6A gene signature, identifying genes with noteworthy prognostic implications. Principal component analysis (PCA) was then employed to construct the m6A-related gene signature, 34 using i as the m6A phenotype-associated genes' expression…”

Section: Generation Of M6a Scorementioning

confidence: 99%

Link between m6A modification and infiltration characterization of tumor microenvironment in lung adenocarcinoma

Yang,

Li,

Zhang

et al. 2023

Exp Biol Med (Maywood)

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N6-methyladenosine (m6A) RNA methylation plays a pivotal role in immune responses and the onset and advancement of cancer. Nonetheless, the precise impact of m6A modification in lung adenocarcinoma (LUAD) and its associated tumor microenvironment (TME) remains to be fully elucidated. Here, we distinguished distinct m6A modification patterns within two separate LUAD cohorts using a set of 21 m6A regulators. The TME characteristics associated with these two patterns align with the immune-inflamed and immune-excluded phenotypes, respectively. We identified 2064 m6A-related genes, which were used as a basis to divide all LUAD samples into three distinct m6A gene clusters. We applied a scoring system to evaluate the m6A gene signature of the m6A modification pattern in individual patients. To authenticate the categorization significance of m6A modification patterns, we established a correlation between m6A score and TME infiltration profiling, tumor somatic mutations, and responses to immunotherapy. A high level of m6A modification may be associated with the aggressiveness and poor prognosis of LUAD. Further studies should investigate the mechanism of action of m6A regulators and m6A-related genes to improve the diagnosis and treatment of patients with LUAD.

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Characterization of m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration in Ovarian Cancer

Cited by 10 publications

References 30 publications

Role of m6A modification in female infertility and reproductive system diseases

Role of m6A modification in female infertility and reproductive system diseases

Ovarian cancer subtypes based on the regulatory genes of RNA modifications: Novel prediction model of prognosis

Link between m6A modification and infiltration characterization of tumor microenvironment in lung adenocarcinoma

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