TY - JOUR
T1 - In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy
AU - Corvigno, Sara
AU - Badal, Sunil
AU - Spradlin, Meredith L.
AU - Keating, Michael
AU - Pereira, Igor
AU - Stur, Elaine
AU - Bayraktar, Emine
AU - Foster, Katherine I.
AU - Bateman, Nicholas W.
AU - Barakat, Waleed
AU - Darcy, Kathleen M.
AU - Conrads, Thomas P.
AU - Maxwell, G. Larry
AU - Lorenzi, Philip L.
AU - Lutgendorf, Susan K.
AU - Wen, Yunfei
AU - Zhao, Li
AU - Thaker, Premal H.
AU - Goodheart, Michael J.
AU - Liu, Jinsong
AU - Fleming, Nicole
AU - Lee, Sanghoon
AU - Eberlin, Livia S.
AU - Sood, Anil K.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85175709621&partnerID=8YFLogxK
U2 - 10.1038/s41698-023-00454-0
DO - 10.1038/s41698-023-00454-0
M3 - Article
C2 - 37923835
AN - SCOPUS:85175709621
SN - 2397-768X
VL - 7
JO - npj Precision Oncology
JF - npj Precision Oncology
IS - 1
M1 - 115
ER -