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. 2023 Dec 12;11(12):3290.
doi: 10.3390/biomedicines11123290.

Genomic Landscape Comparison of Cardiac versus Extra-Cardiac Angiosarcomas

Livia Gozzellino  1 , Margherita Nannini  1   2 , Milena Urbini  3 , Carmine Pizzi  4 , Ornella Leone  5 , Barbara Corti  5 , Chiara Baldovini  5 , Francesco Angeli  1 , Alberto Foà  4 , Davide Pacini  6 , Gianluca Folesani  6 , Alice Costa  7 , Teresa Palumbo  8 , Maria Concetta Nigro  1 , Gianandrea Pasquinelli  9 , Annalisa Astolfi  1   7 , Maria Abbondanza Pantaleo  1   2
Affiliations

Genomic Landscape Comparison of Cardiac versus Extra-Cardiac Angiosarcomas

Livia Gozzellino et al. Biomedicines. .

Abstract

Angiosarcomas (ASs) are rare malignant vascular entities that can affect several regions in our body, including the heart. Cardiac ASs comprise 25-40% of cardiac sarcomas and can cause death within months of diagnosis. Thus, our aim was to identify potential differences and/or similarities between cardiac and extra-cardiac ASs to enhance targeted therapies and, consequently, patients' prognosis. Whole-transcriptome analysis of three cardiac and eleven extra-cardiac non-cutaneous samples was performed to investigate differential gene expression and mutational events between the two groups. The gene signature of cardiac and extra-cardiac non-cutaneous ASs was also compared to that of cutaneous angiosarcomas (n = 9). H/N/K-RAS and TP53 alterations were more recurrent in extra-cardiac ASs, while POTE-gene family overexpression was peculiar to cardiac ASs. Additionally, in vitro functional analyses showed that POTEH upregulation conferred a growth advantage to recipient cells, partly supporting the cardiac AS aggressive phenotype and patients' scarce survival rate. These features should be considered when investigating alternative treatments.

Keywords: bioinformatics; cardiac angiosarcomas; extra-cardiac angiosarcomas; whole-transcriptome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Histological findings representing the L359 and L360 samples. (A) L359: the sheet-like proliferation of round to spindle cells associated with focal necrosis and collagen stroma (hematoxylin–eosin, 200×); (B) L360: epithelioid pattern with high cell proliferation prevalently made up of epithelioid cells with marked nuclear pleomorphism and intracytoplasmic lumina (hematoxylin–eosin, 200×); and (C) L360: immunohistochemistry of neoplastic cells diffusely positive for endothelial marker CD34 (200×).
Figure 2
Figure 2
Unsupervised principal component analysis (PCA) on cardiac angiosarcomas (n = 3) versus extra-cardiac non-cutaneous angiosarcomas (n = 11), showing a close localization of cardiac ASs.
Figure 3
Figure 3
Hierarchical clustering of the most overexpressed gene markers in cardiac (n = 3) versus extra-cardiac non-cutaneous (n = 11) angiosarcomas.
Figure 4
Figure 4
GSEA analysis of enriched pathways in cardiac versus extra-cardiac non-cutaneous angiosarcomas applying the following gene sets: Hallmarks, Reactome, and KEGG. ES: Enrichment Score; NES: Normalized Enrichment Scores; FDR q-val: False Discovery Rate q-value.
Figure 5
Figure 5
(A) GFP expression levels in POTEH-transfected cells (red) versus mock- (green) and pcDNA3.1-transfected (blue) cells. (B) Higher POTEH mRNA expression levels in the POTEH-transfected cells compared with pcDNA3.1-transfected cells (RT-PCR). (C) MTT assay results showing cell viability in pcDNA3.1- and POTEH-transfected cells 48 and 72 h after seeding transfected cells in complete medium (** p < 0.01; *** p < 0.001).
Figure 6
Figure 6
Mutational events classified according to their consequences and occurring in at least 3 samples among cardiac (n = 4), visceral (n = 11), and cutaneous (n = 9) angiosarcomas.
See this image and copyright information in PMC

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