Dataset Information

Clinicopathological and immunological characterization of RNA m⁶ A methylation regulators in ovarian cancer.

ABSTRACT:

Background

N⁶ -methyladenosine (m⁶ A) modification is one of the critical gene regulatory mechanisms implicated in cancer biology. However, the roles of m⁶ A regulators in ovarian cancer are still poorly understood.

Methods

We integrated multiple databases including Gene Expression Omnibus (GEO), ROC Plotter, Kaplan-Meier Plotter, and Tumor Immune Estimation Resource (TIMER) to explore clinicopathological significance of m⁶ A regulators in ovarian cancer.

Results

We showed that alterations in the expression of m⁶ A regulators were related to the malignancy and poor prognosis of ovarian cancer. We found decreased YTHDC1 and increased RBM15 expressions were associated with ovarian cancer cell metastases and HNRNPC was a predictor of paclitaxel resistance. Moreover, dysregulated m⁶ A regulators were enriched in the activation of cancer-related pathways. Our results further demonstrated that the level of immune cell infiltration and the expression of various immune gene markers were closely associated with the expressions of specific m⁶ A regulators (RBM15B, ZC3H13, YTHDF1, and IGF2BP1).

Conclusions

Our study establishes a new prognostic profile of ovarian cancer patients based on m⁶ A regulators, and highlights the potential roles of m⁶ A regulators in ovarian cancer development.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7963423 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Clinicopathological and immunological characterization of RNA m<sup>6</sup> A methylation regulators in ovarian cancer.

Wang Qingying Q Zhang Qinyi Q Li Qingxian Q Zhang Jing J Zhang Jiawen J

Molecular genetics & genomic medicine 20201122 1

<h4>Background</h4>N<sup>6</sup> -methyladenosine (m<sup>6</sup> A) modification is one of the critical gene regulatory mechanisms implicated in cancer biology. However, the roles of m<sup>6</sup> A regulators in ovarian cancer are still poorly understood.<h4>Methods</h4>We integrated multiple databases including Gene Expression Omnibus (GEO), ROC Plotter, Kaplan-Meier Plotter, and Tumor Immune Estimation Resource (TIMER) to explore clinicopathological significance of m<sup>6</sup> A regulators ...[more]

PMID: 33225598

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Project description:N6-methyladenosine (m6A) RNA modification is a reversible mechanism that regulates eukaryotic gene expression. Growing evidence has demonstrated an association between m6A modification and tumorigenesis and response to immunotherapy. However, the overall influence of m6A regulators on the tumor microenvironment and their effect on the response to immunotherapy in lung adenocarcinoma remains to be explored. Here, we comprehensively analyzed the m6A modification patterns of 936 lung adenocarcinoma samples based on 24 m6A regulators. First, we described the features of genetic variation in these m6A regulators. Many m6A regulators were aberrantly expressed in tumors and negatively correlated with most tumor-infiltrating immune cell types. Furthermore, we identified three m6A modification patterns using a consensus clustering method. m6A cluster B was preferentially associated with a favorable prognosis and enriched in metabolism-associated pathways. In contrast, m6A cluster A was associated with the worst prognosis and was enriched in the process of DNA repair. m6A cluster C was characterized by activation of the immune system and a higher stromal cell score. Surprisingly, patients who received radiotherapy had a better prognosis than patients without radiotherapy only in the m6A cluster C group. Subsequently, we constructed an m6A score model that qualified the m6A modification level of individual samples by using principal component analysis algorithms. Patients with high m6A score were characterized by enhanced immune cell infiltration and prolonged survival time and were associated with lower tumor mutation burden and PD-1/CTLA4 expression. The combination of the m6A score and tumor mutation burden could accurately predict the prognosis of patients with lung adenocarcinoma. Furthermore, patients with high m6A score exhibited greater prognostic benefits from radiotherapy and immunotherapy. This study demonstrates that m6A modification is significantly associated with tumor microenvironment diversity and prognosis. A comprehensive evaluation of m6A modification patterns in single tumors will expand our understanding of the tumor immune landscape. In addition, our m6A score model demonstrated that the level of immune cell infiltration plays a significant role in cancer immunotherapy and provides a basis to increase the efficiency of current immune therapies and promote the clinical success of immunotherapy.

Project description:PurposeN6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer.Patients and methodsThe 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis.ResultsResults from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (-) group.ConclusionThe significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.

Dataset Information

Clinicopathological and immunological characterization of RNA m⁶ A methylation regulators in ovarian cancer.

Background

Methods

Results

Conclusions

Publications

Clinicopathological and immunological characterization of RNA m<sup>6</sup> A methylation regulators in ovarian cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Clinicopathological and immunological characterization of RNA m6 A methylation regulators in ovarian cancer.

Background

Methods

Results

Conclusions

Publications

Clinicopathological and immunological characterization of RNA m<sup>6</sup> A methylation regulators in ovarian cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Clinicopathological and immunological characterization of RNA m⁶ A methylation regulators in ovarian cancer.