Journal article
In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy
NPJ precision oncology, Vol.7(1), 115
11/03/2023
DOI: 10.1038/s41698-023-00454-0
PMCID: PMC10624842
PMID: 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.
Details
- Title: Subtitle
- In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy
- Creators
- Sara Corvigno - The University of Texas MD Anderson Cancer CenterSunil Badal - The University of Texas at AustinMeredith L. Spradlin - The University of Texas at AustinMichael Keating - The University of Texas at AustinIgor Pereira - The University of Texas at AustinElaine Stur - The University of Texas MD Anderson Cancer CenterEmine Bayraktar - The University of Texas MD Anderson Cancer CenterKatherine I. Foster - The University of Texas MD Anderson Cancer CenterNicholas W. Bateman - Walter Reed National Military Medical CenterWaleed Barakat - Walter Reed National Military Medical CenterKathleen M. Darcy - Henry M. Jackson FoundationThomas P. Conrads - Walter Reed National Military Medical CenterG. Larry Maxwell - Inova Health SystemPhilip L. Lorenzi - The University of Texas MD Anderson Cancer CenterSusan K. Lutgendorf - University of IowaYunfei Wen - The University of Texas MD Anderson Cancer CenterLi Zhao - Houston, TX USAPremal H. Thaker - Washington University in St. LouisMichael J. Goodheart - University of IowaJinsong Liu - The University of Texas MD Anderson Cancer CenterNicole Fleming - The University of Texas MD Anderson Cancer CenterSanghoon Lee - The University of Texas MD Anderson Cancer CenterLivia S. Eberlin - Baylor College of MedicineAnil K. Sood - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- NPJ precision oncology, Vol.7(1), 115
- DOI
- 10.1038/s41698-023-00454-0
- PMID
- 37923835
- PMCID
- PMC10624842
- NLM abbreviation
- NPJ Precis Oncol
- ISSN
- 2397-768X
- eISSN
- 2397-768X
- Publisher
- Nature Publishing Group UK
- Grant note
- ;
- Language
- English
- Date published
- 11/03/2023
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984507027002771
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