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Obesity Is Associated with Altered Tumor Metabolism in Metastatic Melanoma.
Hahn, Andrew W; Menk, Ashley V; Rivadeneira, Dayana B; Augustin, Ryan C; Xu, Mingchu; Li, Jun; Wu, Xiaogang; Mishra, Aditya K; Gide, Tuba N; Quek, Camelia; Zang, Yan; Spencer, Christine N; Menzies, Alexander M; Daniel, Carrie R; Hudgens, Courtney W; Nowicki, Theodore; Haydu, Lauren E; Khan, M A Wadud; Gopalakrishnan, Vancheswaran; Burton, Elizabeth M; Malke, Jared; Simon, Julie M; Bernatchez, Chantale; Putluri, Nagireddy; Woodman, Scott E; Vashisht Gopal, Y N; Guerrieri, Renato; Fischer, Grant M; Wang, Jian; Wani, Khalida M; Thompson, John F; Lee, Jeffrey E; Hwu, Patrick; Ajami, Nadim; Gershenwald, Jeffrey E; Long, Georgina V; Scolyer, Richard A; Tetzlaff, Michael T; Lazar, Alexander J; Schadendorf, Dirk; Wargo, Jennifer A; Kirkwood, John M; DeBerardinis, Ralph J; Liang, Han; Futreal, Andrew; Zhang, Jianhua; Wilmott, James S; Peng, Weiyi; Davies, Michael A; Delgoffe, Greg M.
Afiliação
  • Hahn AW; Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Menk AV; Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Rivadeneira DB; Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Augustin RC; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Xu M; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Li J; Department of Bioinformatics and Computational Biology, Division of Basic Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Wu X; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Mishra AK; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Gide TN; Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Quek C; Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Zang Y; Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • Spencer CN; Parker Institute for Cancer Immunotherapy, San Francisco, California.
  • Menzies AM; Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Daniel CR; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Hudgens CW; Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Nowicki T; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
  • Haydu LE; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.
  • Khan MAW; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California.
  • Gopalakrishnan V; Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Burton EM; Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Malke J; Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Simon JM; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Bernatchez C; Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Putluri N; Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Woodman SE; Department of Biologics Development, Division of Therapeutics Discovery, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Vashisht Gopal YN; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
  • Guerrieri R; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Fischer GM; Department of Melanoma Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Wang J; Department of Melanoma Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Wani KM; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
  • Thompson JF; Department of Biostatistics, Division of Biosciences, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Lee JE; Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Hwu P; Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Ajami N; Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Gershenwald JE; Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa Bay, Florida.
  • Long GV; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Scolyer RA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California.
  • Tetzlaff MT; Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Lazar AJ; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Schadendorf D; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
  • Wargo JA; Melanoma Institute of Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Kirkwood JM; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • DeBerardinis RJ; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
  • Liang H; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia.
  • Futreal A; Division of Dermatopathology, Department of Pathology, University of California San Francisco, San Francisco, California.
  • Zhang J; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Wilmott JS; Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Peng W; Department of Dermatology, Venereology, and Allergology, University Hospital Essen and German Cancer Consortium, Partner site Essen, Germany.
  • Davies MA; Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Delgoffe GM; Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res ; 29(1): 154-164, 2023 01 04.
Article em En | MEDLINE | ID: mdl-36166093
ABSTRACT

PURPOSE:

Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI). EXPERIMENTAL

DESIGN:

Associations between BMI [normal (NL < 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371).

RESULTS:

DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased central carbon metabolism in OW/OB metastatic melanoma tumors and patient-derived cell lines. The overall structure, diversity, and taxonomy of the fecal microbiome did not differ by BMI.

CONCLUSIONS:

These findings suggest that the host metabolic phenotype influences melanoma metabolism and provide insight into the improved outcomes observed in OW/OB patients with metastatic melanoma treated with ICIs and targeted therapies. See related commentary by Smalley, p. 5.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Segunda Neoplasia Primária / Melanoma Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Segunda Neoplasia Primária / Melanoma Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article