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In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy.
Corvigno, Sara; Badal, Sunil; Spradlin, Meredith L; Keating, Michael; Pereira, Igor; Stur, Elaine; Bayraktar, Emine; Foster, Katherine I; Bateman, Nicholas W; Barakat, Waleed; Darcy, Kathleen M; Conrads, Thomas P; Maxwell, G Larry; Lorenzi, Philip L; Lutgendorf, Susan K; Wen, Yunfei; Zhao, Li; Thaker, Premal H; Goodheart, Michael J; Liu, Jinsong; Fleming, Nicole; Lee, Sanghoon; Eberlin, Livia S; Sood, Anil K.
Afiliación
  • Corvigno S; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Badal S; Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
  • Spradlin ML; Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
  • Keating M; Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
  • Pereira I; Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
  • Stur E; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Bayraktar E; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Foster KI; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Bateman NW; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Barakat W; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  • Darcy KM; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Conrads TP; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  • Maxwell GL; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Lorenzi PL; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  • Lutgendorf SK; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Wen Y; Women's Health Integrated Research Center, Women's Service Line, Inova Health System, Falls Church, VA, USA.
  • Zhao L; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA.
  • Thaker PH; Women's Health Integrated Research Center, Women's Service Line, Inova Health System, Falls Church, VA, USA.
  • Goodheart MJ; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Liu J; Departments of Psychological and Brain Sciences, Obstetrics and Gynecology, and Urology, University of Iowa, Iowa City, IA, USA.
  • Fleming N; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lee S; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Eberlin LS; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University, St. Louis, MO, USA.
  • Sood AK; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Iowa, Iowa City, IA, USA.
NPJ Precis Oncol ; 7(1): 115, 2023 Nov 03.
Article en En | MEDLINE | ID: mdl-37923835
ABSTRACT
In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline hydroxylation of hypoxia-inducible factor alpha in the stromal regions. Metabolites more abundant in the epithelial regions of post-NACT PR tumors were involved in the metabolism of nucleotides, and metabolites more abundant in the stromal regions of post-NACT PR tumors were related to aspartate and asparagine metabolism, phenylalanine and tyrosine metabolism, nucleotide biosynthesis, and the urea cycle. A predictive model built on ions with differential abundances allowed the classification of patients' tumor responses as ER or PR with 75% accuracy (10-fold cross-validation ridge regression model). These findings offer new insights related to differential responses to chemotherapy and could lead to novel actionable targets.

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos