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. 2021 Jan 18;14(1):32-41.
doi: 10.18240/ijo.2021.01.05. eCollection 2021.

A multi-omics study on cutaneous and uveal melanoma

Qi Zhang  1 , Ze-Nan Lin  2 , Jie Chen  3 , Wen-Xu Zheng  4
Affiliations

A multi-omics study on cutaneous and uveal melanoma

Qi Zhang et al. Int J Ophthalmol. .

Abstract

Aim: To present the multi-omics landscape of cutaneous melanoma (CM) and uveal melanoma (UM) from The Cancer Genome Atlas (TCGA).

Methods: The differentially expressed genes (DEGs) between CM and UM were found and integrated into a gene ontology enrichment analysis. Besides, the differentially expressed miRNAs were also identified. We also compared the methylation level of CM with UM and identified the differentially methylated regions to integrate with the DEGs to display the relationship between the gene expression and DNA methylation. The differentially expressed transcription factors (TFs) were identified.

Results: Though CM had more mutational burden than UM, they shared several similarities such as the same rankings in diverse variant types. Except GNAQ and GNA11, the other top 18 mutated genes of the combined group were mostly detected in CM instead of UM. On the transcriptomic level, 4610 DEGs were found and integrated into a gene ontology enrichment analysis. We also identified 485 differentially expressed miRNAs. The methylation analysis showed that UM had a significantly higher methylation level than CM. The integration of differentially methylated regions and DEGs demonstrated that most DEGs were downregulated in UM and the hypo- and hypermethylation presented no obvious difference within these DEGs. Finally, 116 hypermethylated TFs and 114 hypomethylated TFs were identified as differentially expressed TFs in CM when compared with UM.

Conclusion: This multi-omics study on comparing CM with UM confirms that they differ in all analyzed levels. Of notice, the results also offer new insights with implications for elucidating certain unclear problems such as the distinct role of epithelial mesenchymal transition in two melanomas, the different metastatic routes of CM and UM and the liver tropism of metastatic UM.

Keywords: cutaneous melanoma; epigenetics; genomics; transcriptomics; uveal melanoma.

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Figures

Figure 1
Figure 1. Multiple genomic alteration analysis of CM
A: The counts of 3 variant types; B: The counts of 5 gene variant classifications; C: The variants' counts of 6 SNP classes; D: The variants' counts per CM sample; E: The summary of 5 gene variant classification: box plots show median counts and the interquartile range; F: Top 10 most frequently mutated genes in the CM group.
Figure 2
Figure 2. Multiple genomic alteration analysis of uveal melanoma
A: The counts of 3 variant types; B: The counts of 9 gene variant classifications; C: The variants' counts of 6 SNP classes; D: The variants' counts per UM sample; E: The summary of 9 gene variant classification: box plots show median counts and the interquartile range; F: Top 10 most frequently mutated genes in the UM group.
Figure 3
Figure 3. Top 20 most frequently mutated genes in the combined group of CM and UM
The upper histogram shows the variants' counts per sample. The percentiles at the left border of the main heatmap mean the occurrence ratio of each gene mutation. The right horizontal histogram presents the variant classifications of each gene. The covariate tracks show clusters for disease, gender, race and variant classification type.
Figure 4
Figure 4. DNA methylation landscape across all CM and UM samples
The heatmap shows the DNA methylation levels across CM and UM samples. Covariate tracks show the subtypes of diseases, genders, vital statuses and races.
Figure 5
Figure 5. Starburst plot based on the differentially methylated CpG sites and nearby genes
DNA methylation [log10(FDR-corrected P-value)] and DEGs' expression [log10(FDR-corrected P-value)] were plotted on the x-axis and y-axis, respectively. Both of the horizontal and vertical black dashed lines presented an FDR-adjusted P value of 10−5.
See this image and copyright information in PMC

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