Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes.

Autor:	Mirhadi S; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Tam S; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Li Q; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Moghal N; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Pham NA; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Tong J; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, Canada., Golbourn BJ; John G. Rangos Sr. Research Center, Children's Hospital of Pittsburgh, and Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Krieger JR; SPARC BioCentre, Hospital for Sick Children, Toronto, ON, Canada., Taylor P; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, Canada., Li M; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Weiss J; Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada., Martins-Filho SN; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Raghavan V; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Mamatjan Y; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Khan AA; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, Canada., Cabanero M; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Sakashita S; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Huo K; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Agnihotri S; John G. Rangos Sr. Research Center, Children's Hospital of Pittsburgh, and Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Ishizawa K; Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada., Waddell TK; Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada.; Department of Surgery, University of Toronto, Toronto, ON, Canada., Zadeh G; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Surgery, University of Toronto, Toronto, ON, Canada., Yasufuku K; Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada.; Department of Surgery, University of Toronto, Toronto, ON, Canada., Liu G; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Medicine, Division of Medical Oncology, University of Toronto, Toronto, ON, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada., Shepherd FA; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Medicine, Division of Medical Oncology, University of Toronto, Toronto, ON, Canada., Moran MF; Program in Cell Biology, Hospital for Sick Children, Toronto, ON, Canada. m.moran@utoronto.ca.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. m.moran@utoronto.ca.; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. m.moran@utoronto.ca., Tsao MS; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. ming.tsao@uhn.ca.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. ming.tsao@uhn.ca.; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. ming.tsao@uhn.ca.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2022 Apr 05; Vol. 13 (1), pp. 1811. Date of Electronic Publication: 2022 Apr 05.
DOI:	10.1038/s41467-022-29444-9
Abstrakt:	Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbor actionable driver mutations and there is an urgent need for patient-derived model systems that will enable the development of new targeted therapies. NSCLC and other cancers display profound proteome remodeling compared to normal tissue that is not predicted by DNA or RNA analyses. Here, we generate 137 NSCLC patient-derived xenografts (PDXs) that recapitulate the histology and molecular features of primary NSCLC. Proteome analysis of the PDX models reveals 3 adenocarcinoma and 2 squamous cell carcinoma proteotypes that are associated with different patient outcomes, protein-phosphotyrosine profiles, signatures of activated pathways and candidate targets, and in adenocarcinoma, stromal immune features. These findings portend proteome-based NSCLC classification and treatment and support the PDX resource as a viable model for the development of new targeted therapies. (© 2022. The Author(s).)
Databáze:	MEDLINE
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