Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis

Abstract

Objective. Platinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic signatures that predict platinum resistance in patients receiving chemotherapy for gynecologic cancers.Methods. In this study 47 patients with adenocarcinoma of the ovary or uterus who were candidates for carboplatin plus paclitaxel submitted blood for quantitation of metabolites and surgical specimens for the Gynecologic Oncology xxx (xxxx) xxx

Amino Acid-Metabolizing Enzymes in Advanced High-Grade Serous Ovarian Cancer Patients: Value of Ascites as Biomarker Source and Role for IL4I1 and IDO1

“…Moreover, in contrast to the reported ARG1 expression in ovarian cancer, indications for increased ARG1 activity were not found either. Instead, our findings of decreased Orn and Cit levels in the ovarian cancer patients correlate with other studies showing decreased levels of these metabolites in patient plasma or serum samples [58,59]. Together with the elevated Arg levels, these changes may signify enhanced Arg synthesis rather than metabolism, since Arg is (in)directly synthesized from Orn and Cit.…”

Diagnostic and Prognostic Performance of Metabolic Signatures in Pancreatic Ductal Adenocarcinoma: The Clinical Application of Quantitative NextGen Mass Spectrometry

“…The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/metabo14030148/s1, Table S1: Clinical characteristics of PDAC patients; Table S2: Clinical characteristics of controls; Table S3:The AbsoluteIDQ®p180 kit by Biocrates AG Life Sciences with all of the analytes and their standard nomenclature; Figure S1: A depicting the ratio of (C5-M-DC/PC ae C40:1) to C5:1-DC in plasma from patients with pancreatic cancer (PanCA) and normal healthy controls (Controls); Figure S8: PCA unsupervised analysis where pancreatic cancer (PDAC) samples were analyzed against other malignant conditions: liver cancer (30), lung cancer (23), colon cancer (85), head/neck cancer (58), hematologic cancer (65),breast cancer (58); and against samples from patients with non-malignant metabolic and immunological chronic conditions: latest ages of metabolic syndrome (70),HCV-induced cirrhosis (30); hyperthyroidism (8); hypothyroidism (8); HIVinfection (18); polycystic ovary syndrome (49); autoimmunedisease (86)…”

“…As we have shown in breast [ 17 ] and ovarian [ 18 ] cancers, comprehensive profiling of cancer-related metabolic alterations offers diagnostic, prognostic and predictive insights that can inform clinical therapy decisions. As genotypes translate into phenotypes through intricate metabolic networks, metabolomics has the potential to offer a powerful tool to interrogate the complexity of pancreatic cancer biology [ 19 , 20 , 21 , 22 ].…”

Patient-Derived Organoids: The Beginning of a New Era in Ovarian Cancer Disease Modeling and Drug Sensitivity Testing

“…Mean cisplatin lethal concentration 50% (LC50) was associated with a non-significant decrease in complete remission, reduced DFS as well as biochemical signatures of numerous metabolites. Interestingly, receiver operating curves (ROC) of lipid ratios, branched chain amino acids and the tryptophan to kynurenine ratio represented highly sensitive and specific tools for the identification of patients at the highest risk of relapse and death [56]. Gorski et al utilized six HGSOC tumor organoid lines to screen for carboplatin sensitivity at different doses and found the organoid line UK1254 to be resistant to carboplatin and have a significantly shorter progression-free survival (PFS), with subsequent gene expression analysis identifying the interplay between various pathways related to nuclear factor kappa B (NFκB), PRDM6 or Phosphoinositide-3-Kinase Adaptor Protein 1 (PI3KAP1) activation [57].…”