BACKGROUND The contribution of tryptophan (TRP) metabolism via the kynurenine (KP) and serotonin (SP) pathways in GBM biology has recently seen a growing interest. This study aims to address the association between pre-operative peripheral blood levels of TRP, kynurenine (KYN), 5-hydroxy-tryptophan (5-HTP), and serotonin (5-HT) and relevant oncological outcomes in GBM IDH-wt patients. MATERIAL AND METHODS A total of 62 adult patients undergoing maximal safe resection of newly diagnosed glioblastoma WHO grade 4 IDH-wt (GBM) were included. The variables were dichotomized and analyzed to explore their single contributions in building a predictive model of overall survival (OS) and progression-free survival (PFS) in GBM patients. RESULTS The mean baseline serum levels of 5-HT, KYN, 5-HTP, and 5-HT/TRP were significantly lower (-76%, -87%, -76%, -75%, p<0.001 respectively) in GBM patients when compared to n=27 healthy individuals. The median OS in the whole cohort of GBM patients was 16.3 months (95% CI:13.4-21.7). Patients with 5-HT < 78 ng/mL had a median OS of 14.4 months (95% CI: 11.4-17.6) compared to 22.5 (95% CI:17.7-27) in patients with 5-HT > 78 ng/mL (p = 0.01). Shorter OS was recorded in patients with KYN < 18 ng/mL (9.8, 95% CI:11.4-17.6 vs 17.5 months, 95% CI:14.4-22.5, p=0.002), KYN/TRP < 2.55 (13.4, 95% CI:11.4-15.6 vs 19.1 months, 95% CI:14.0-28.6, p=0.002), 5-HTP/TRP < 0.89 (11.5, 95% CI:10.9-20.6 vs 17.6 months 95% CI:14.4-32.4, p=0.02), and 5-HT/TRP < 5.78 (13.4, 95% CI: 11.4-15.6 vs 19.1 months, 95% CI: 14.0-28.6, p=0.002)The median PFS was 9.27 months (95% CI:7.77-13.9). Significantly shorter PFS was observed in patients with 5-HT < 78 ng/mL (p=0.04), KYN < 18 ng/mL (p=0.02), 5-HT/TRP < 5.78 (p=0.001), KYN/TRP < 2.55 (p=0.005). Multivariate Cox analysis (R2=67%) confirmed an independent predictive role for poor OS of decreased KYN (p=0.001), 5-HTP (p<0.001) and 5-HT (p<0.001). Similarly, decreased 5-HT (p=0.004), and decreased 5-HTP (p=0.01) were predictive of poorer PFS. CONCLUSION This study highlights an intriguing association between enhanced degradation of TRP into KYN at the expense of the amount of the amino acid for the SP and median survival times in GBM. Decreased levels of KYN, 5-HTP, and 5-HT were associated with shorter OS.
Preoperative peripheral blood serotonin and kynurenine levels are associated with oncological outcomes in glioblastoma IDH-wt patients / De Domenico, P; Snider, S; Comai, S; Bertazzo, A; Nasini S., Barzon B; Ruban, A; Roncelli, F; Mortini, P; Gagliardi, F.. - 26:supplement_5(2024), p. v49. ( 19th meeting of the European Association of Neuro-Oncology (EANO) Glasgow, UK 17-20 Oct 2024) [10.1093/neuonc/noae144.157].
Preoperative peripheral blood serotonin and kynurenine levels are associated with oncological outcomes in glioblastoma IDH-wt patients
De Domenico P
Primo
;Comai S;Roncelli F;Mortini P;
2024-01-01
Abstract
BACKGROUND The contribution of tryptophan (TRP) metabolism via the kynurenine (KP) and serotonin (SP) pathways in GBM biology has recently seen a growing interest. This study aims to address the association between pre-operative peripheral blood levels of TRP, kynurenine (KYN), 5-hydroxy-tryptophan (5-HTP), and serotonin (5-HT) and relevant oncological outcomes in GBM IDH-wt patients. MATERIAL AND METHODS A total of 62 adult patients undergoing maximal safe resection of newly diagnosed glioblastoma WHO grade 4 IDH-wt (GBM) were included. The variables were dichotomized and analyzed to explore their single contributions in building a predictive model of overall survival (OS) and progression-free survival (PFS) in GBM patients. RESULTS The mean baseline serum levels of 5-HT, KYN, 5-HTP, and 5-HT/TRP were significantly lower (-76%, -87%, -76%, -75%, p<0.001 respectively) in GBM patients when compared to n=27 healthy individuals. The median OS in the whole cohort of GBM patients was 16.3 months (95% CI:13.4-21.7). Patients with 5-HT < 78 ng/mL had a median OS of 14.4 months (95% CI: 11.4-17.6) compared to 22.5 (95% CI:17.7-27) in patients with 5-HT > 78 ng/mL (p = 0.01). Shorter OS was recorded in patients with KYN < 18 ng/mL (9.8, 95% CI:11.4-17.6 vs 17.5 months, 95% CI:14.4-22.5, p=0.002), KYN/TRP < 2.55 (13.4, 95% CI:11.4-15.6 vs 19.1 months, 95% CI:14.0-28.6, p=0.002), 5-HTP/TRP < 0.89 (11.5, 95% CI:10.9-20.6 vs 17.6 months 95% CI:14.4-32.4, p=0.02), and 5-HT/TRP < 5.78 (13.4, 95% CI: 11.4-15.6 vs 19.1 months, 95% CI: 14.0-28.6, p=0.002)The median PFS was 9.27 months (95% CI:7.77-13.9). Significantly shorter PFS was observed in patients with 5-HT < 78 ng/mL (p=0.04), KYN < 18 ng/mL (p=0.02), 5-HT/TRP < 5.78 (p=0.001), KYN/TRP < 2.55 (p=0.005). Multivariate Cox analysis (R2=67%) confirmed an independent predictive role for poor OS of decreased KYN (p=0.001), 5-HTP (p<0.001) and 5-HT (p<0.001). Similarly, decreased 5-HT (p=0.004), and decreased 5-HTP (p=0.01) were predictive of poorer PFS. CONCLUSION This study highlights an intriguing association between enhanced degradation of TRP into KYN at the expense of the amount of the amino acid for the SP and median survival times in GBM. Decreased levels of KYN, 5-HTP, and 5-HT were associated with shorter OS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
