RNA-sequencing predicts a role of androgen receptor and aldehyde dehydrogenase 1A1 in osteosarcoma lung metastases.

Autor: Heim TE; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA. teh39@pitt.edu., Hankins ML; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Belayneh R; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Douglas N; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Dinh V; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Kovvur M; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Boone DN; University of Pittsburgh Department of Biomedical Informatics, Pittsburgh, PA, USA., Ukani V; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Bhogal S; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Patel V; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Moniz TMA; Columbia University with Trinity College, Dublin, UK.; UPMC Hillman Cancer Center Academy, Pittsburgh, PA, USA., Bailey KM; University of Pittsburgh School of Medicine, Department of Pediatrics, Pittsburgh, PA, USA., John I; University of Pittsburgh Department of Pathology, Pittsburgh, PA, USA., Schoedel K; University of Pittsburgh Department of Pathology, Pittsburgh, PA, USA., Weiss KR; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA., Watters RJ; University of Pittsburgh Department of Orthopaedic Surgery, Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2024 Mar; Vol. 43 (14), pp. 1007-1018. Date of Electronic Publication: 2024 Feb 15.
DOI: 10.1038/s41388-024-02957-x
Abstrakt: One-third of pediatric patients with osteosarcoma (OS) develop lung metastases (LM), which is the primary predictor of mortality. While current treatments of patients with localized bone disease have been successful in producing 5-year survival rates of 65-70%, patients with LM experience poor survival rates of only 19-30%. Unacceptably, this situation that has remained unchanged for 30 years. Thus, there is an urgent need to elucidate the mechanisms of metastatic spread in OS and to identify targetable molecular pathways that enable more effective treatments for patients with LM. We aimed to identify OS-specific gene alterations using RNA-sequencing of extremity and LM human tissues. Samples of extremity and LM tumors, including 4 matched sets, were obtained from patients with OS. Our data demonstrate aberrant regulation of the androgen receptor (AR) pathway in LM and predicts aldehyde dehydrogenase 1A1 (ALDH1A1) as a downstream target. Identification of AR pathway upregulation in human LM tissue samples may provide a target for novel therapeutics for patients with LM resistant to conventional chemotherapy.
(© 2024. The Author(s).)
Databáze: MEDLINE
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