Metastasis‐associated <scp>microRNA</scp> expression in canine uveal melanoma

Starkey, Mike; Compston‐Garnett, L.; Malho, Pedro; Dunn, Kelli Bullard; Dubielzig, Richard R.

doi:10.1111/vco.12315

Cited by 24 publications

(25 citation statements)

References 67 publications

(80 reference statements)

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“…However, only 1 to 2 % of the transcripts have the capacity for protein translation. [11][12][13] In fact, post-transcriptional regulation at the RNA level through cis-and trans-mechanisms is essential to control the gene expression procedures that determine cellular function and cell fate. [14] To date, more than 150 chemical modi cations have been described for RNA.…”

Section: Discussionmentioning

confidence: 99%

The prognostic values of m6A RNA methylation regulators in Uveal melanoma

Tang

Wan

2020

Preprint

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Abstract Purpose: The aim of this study was to identify gene signatures and prognostic values of m6A methylation regulators in uveal melanoma (UM). Methods: The RNA sequencing dataset and corresponding clinical information were downloaded from TCGA and GEO database. Based on the expression of m6A RNA methylation regulators , the patients were further clustered into different groups by applying the “ClassDiscovery” algorithm. Best survival analysis was performed to select prognostic m6A regulators and multivariate cox regression analysis was applied to constructed m6A regulators signature. The association between mutations and m6A regulators was assessed by Kruskal−Wallis tests and clinical characteristics were examined by using chi-square test. Result: Totally, we identified two molecular subtypes of UM (C1/2) by applying consensus clustering to m6A RNA methylation regulators. In contrast to the C1 subtype, the C2 subtype associates with a better prognosis, have higher percentage of subtype 1 and lower percentage of Monosomy 3 which have been regarded as the well established prognostic markers for UM. The malignant hallmarks of mTORC1 signaling, oxidative phosphorylation, interferon-a response and apoptosis signaling are also significantly enriched in the C1 subtype. Moreover, a 3 - m6A regulators signature was constructed by multivariate cox regression analysis method, which closely correlated with chromosome 3 status, subtype 1 of UM and can robustly predict patients’ overall survival time. Conclusions: m6A RNA methylation regulators take a crucial role in the potential malignant progression and prognostic value of UM and might be regarded as a new promising biomarker for UM prognosis and treatment strategy development.

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Section: Discussionmentioning

confidence: 99%

The prognostic values of m6A RNA methylation regulators in Uveal melanoma

Tang

Wan

2020

Preprint

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Section: Discussionmentioning

confidence: 99%

The prognostic values of m6A RNA methylation regulators in Uveal melanoma

Wan

Tang

2019

Preprint

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Purpose The aim of this study were to identify gene signatures and prognostic values of m6A methylation regulators in uveal melanoma (UM). Methods The RNA sequencing dataset and corresponding clinical information were downloaded from TCGA and GEO database. Based on the expression of m6A RNA methylation regulators, the patients were further clustered into different groups by applying the “ClassDiscovery” algorithm. Survival analysis was performed using log-rank tests and LASSO regression model. The association between mutations and m6A regulators was assessed by student t tests and clinical characteristics was examined by using chi-square test. Result Totally, we identified two molecular subtypes of UM (C1/2) by applying consensus clustering to m6A RNA methylation regulators. Contrasted to the C1 subtype, the C2 subtype associates with a better prognosis, longer survival time and lower percentage of Monosomy 3. The malignant hallmarks of mTORC1 signaling, oxidative phosphorylation, interferon-a response and apoptosis signaling are also significantly enriched in the C1 subtype. Moreover, a 2-m6A regulators signature was screened out by LASSO method, which can robustly predict UM patients survival. Conclusions m6A RNA methylation regulators take a crucial role in the potential malignant progression and prognostic value of UM and might be regarded as a new promising biomarker for UM prognosis and treatment strategy development.

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“…The demonstration that gene expression signatures of metastatic potential could be detected in primary human tumours [12] lead to the identification of metastasis-associated gene expression signatures by comparison of gene expression in human primary tumours that did and did not metastasise [13,14]. Veterinary researchers have performed similar comparisons of metastasising and non-metastasising primary tumours to identify molecular genetic and epigenetic events associated with canine tumour metastasis, both as targets for anti-metastatic therapeutics and potential prognostic biomarkers [15][16][17][18][19]. Such studies will expedite the identification of potential targets for drugs aimed at preventing human tumour metastasis by strengthening the 'candidature', as a target, of genes that are associated with the metastasis of a given tumour in both humans and dogs.…”

Section: Advantages Of Involving Companion Canines In the Developmentmentioning

confidence: 99%