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GDF-15 is a biomarker of aggressiveness and is down-regulated by the mTOR inhibitor sirolimus through ATF4 and ATF5 suppression in epithelioid hemangioendothelioma.

ABSTRACT: Growth and differentiation factor-15 (GDF-15), a member of the TGF-β superfamily, exhibits elevated expression in various tumor types, often linked to disease aggressiveness. In this study, which used patient-derived xenografts and paired cell lines of epithelioid hemangioendothelioma (EHE), it was found that EHE cells produce and release GDF-15. Furthermore, the mTOR inhibitor sirolimus was observed to inhibit GDF-15 expression and release by down-regulating ATF4 and ATF5 transcription factors. To assess the clinical relevance of GDF-15 in EHE, which can manifest as both relatively indolent and exceptionally aggressive forms, circulating GDF-15 levels were assessed in two independent cohorts of EHE patients, one retrospective and one prospective. The results provided evidence of an association between circulating GDF-15 levels and the aggressiveness of EHE. In summary, these findings suggest that GDF-15 can serve as a biomarker for EHE aggressiveness and may have implications for monitoring the effectiveness of sirolimus in EHE patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246235 | GEO | 2024/04/24

REPOSITORIES: GEO

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GDF-15 is a biomarker of aggressiveness and is down-regulated by the mTOR inhibitor sirolimus through ATF4 and ATF5 suppression in epithelioid hemangioendothelioma.

Project description:Growth and differentiation factor-15 (GDF-15), a member of the TGF-β superfamily, exhibits elevated expression in various tumor types, often linked to disease aggressiveness. In this study, which used patient-derived xenografts and paired cell lines of epithelioid hemangioendothelioma (EHE), it was found that EHE cells produce and release GDF-15. Furthermore, the mTOR inhibitor sirolimus was observed to inhibit GDF-15 expression and release by down-regulating ATF4 and ATF5 transcription factors. To assess the clinical relevance of GDF-15 in EHE, which can manifest as both relatively indolent and exceptionally aggressive forms, circulating GDF-15 levels were assessed in two independent cohorts of EHE patients, one retrospective and one prospective. The results provided evidence of an association between circulating GDF-15 levels and the aggressiveness of EHE. In summary, these findings suggest that GDF-15 can serve as a biomarker for EHE aggressiveness and may have implications for monitoring the effectiveness of sirolimus in EHE patients.

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