Evaluating fingerprints for clear cell renal cell carcinoma prognosis

NICOLAS ZABALEGUI; MAXIMILIAN REY; MALENA MANZI; RIQUELME, GABRIEL; MARIA EUGENIA MONGE

Conferencia; 18th Annual Conference of the Metabolomics Society; 2022

Kidney cancer is a disease of dysregulated cellular metabolism. Renal cell carcinoma (RCC) is themain type of kidney cancer with more than 50% of cases incidentally diagnosed. Surgery is the mostpromising treatment for curation when the disease is detected at early stages, since it is inherentlyresistant to chemotherapy and radiotherapy. Clear cell RCC (ccRCC) is the most common histologicalsubtype, and is characterized for being a glycolytic and lipogenic tumor, exhibiting abnormalcholesterol metabolism and fat storage. Our research group has recently analyzed serum samplesfrom a cohort comprised of ccRCC patients with different stages (I, II, III, IV; n=112) and healthyindividuals (n=52) with a coupled untargeted UHPLC-HRMS-based lipidomics machine learningapproach. [1] A 16-lipid panel, including cholic acid, undecylenic acid, lauric acid, linoleic acid,LPC(16:0/0:0), and PC(18:2/18:2), allowed discriminating ccRCC patients from healthy individuals with77.1% accuracy in an independent test set.[1] This panel was further evaluated as a signature formetabolic response after nephrectomy in paired-serum samples. Changes in the lipid signature ofsamples collected before and after surgery were investigated, and were compared with thosefingerprints obtained from healthy individuals. Results suggest that ccRCC-associated lipidphenotypes may be used for evaluating the metabolic phenoreversion to a healthy metabolic state,and contribute to patient prognosis stratification. Currently, we are evaluating the feasibility ofdetecting this lipid panel and its discrimination capability for ccRCC diagnosis and prognosis usinghigh-throughput analytical methods based on Direct Analysis in Real Time (DART)-QTOF-MS. Otherlipids potentially relevant for disease diagnosis and prognosis might also be considered as well.Serum samples were provided by the Argentine Public Oncologic Serum Biobank “Biobanco Públicode Muestras Séricas Oncológicas” from “Instituto de Oncología A. H. Roffo”.