A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms.
Ann Surg Oncol
; 30(8): 5132-5141, 2023 Aug.
Article
en En
| MEDLINE
| ID: mdl-37149550
ABSTRACT
BACKGROUND:
There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma.METHODS:
Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes.RESULTS:
Eight peritoneal tumor samples were obtained and analyzed LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate.CONCLUSIONS:
Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias del Apéndice
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Neoplasias Peritoneales
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Seudomixoma Peritoneal
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Adenocarcinoma
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Adenocarcinoma Mucinoso
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
Ann Surg Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article