Background: In recent years, there has been a growing interest in exploring the potential contribution of tryptophan (TRP) metabolism via the kynurenine (KP) and serotonin (SP) pathways in Glioblastoma (GBM) biology. 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. Methods: This is a single-center, retrospective clinical study. Serum from 62 adult patients undergoing maximal safe resection of newly diagnosed glioblastoma WHO-grade 4 IDH-wt (GBM) and n = 27 healthy controls were analyzed. The variables of interest were dichotomized via maximally selected rank statistics. Kaplan Meier and Cox multivariate regression analysis were conducted to explore the single contributions of these parameters in building a predictive model of overall survival (OS) and progression-free survival (PFS) in these patients. Results: The mean baseline serum levels of 5-HT, KYN, and 5-HTP were significantly lower in GBM when compared to n = 27 healthy individuals (P <.001). Patients with 5-HT <78 ng/mL had a median OS of 14.4 months compared to 22.5 months in patients with increased levels (P =.01). Shorter OS was observed in patients with KYN <18 ng/mL (9.8 vs 17.5 months, P =.002), KYN/TRP <2.55 (11.4 vs 17.1, P =.002), 5-HTP/TRP <0.89 (11.5 vs 17.6 months, P =.02), and 5-HT/TRP <5.78 (13.4 vs 19.1 months, P =.002) compared to patients with high levels. Shorter PFS in patients with 5-HT <78 ng/mL (P =.04), KYN <18 ng/mL (P =.02), 5-HT/TRP <5.78 (P =.001), KYN/TRP <2.55 (P =.005). Reduced KYN, 5-HTP, and 5-HT were independent predictors of poor OS. Conclusions: This study highlights an intriguing association between the degradation of TRP along the KP and SP and median survival times in GBM. Decreased KYN, 5-HTP, and 5-HT levels were associated with shorter OS.
Preoperative Peripheral Blood Serotonin and Kynurenine Levels Are Associated With Oncological Outcomes in Glioblastoma IDH-wt Patients
Comai, Stefano;Bertazzo, Antonella;Barzon, Benedetta;
2025
Abstract
Background: In recent years, there has been a growing interest in exploring the potential contribution of tryptophan (TRP) metabolism via the kynurenine (KP) and serotonin (SP) pathways in Glioblastoma (GBM) biology. 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. Methods: This is a single-center, retrospective clinical study. Serum from 62 adult patients undergoing maximal safe resection of newly diagnosed glioblastoma WHO-grade 4 IDH-wt (GBM) and n = 27 healthy controls were analyzed. The variables of interest were dichotomized via maximally selected rank statistics. Kaplan Meier and Cox multivariate regression analysis were conducted to explore the single contributions of these parameters in building a predictive model of overall survival (OS) and progression-free survival (PFS) in these patients. Results: The mean baseline serum levels of 5-HT, KYN, and 5-HTP were significantly lower in GBM when compared to n = 27 healthy individuals (P <.001). Patients with 5-HT <78 ng/mL had a median OS of 14.4 months compared to 22.5 months in patients with increased levels (P =.01). Shorter OS was observed in patients with KYN <18 ng/mL (9.8 vs 17.5 months, P =.002), KYN/TRP <2.55 (11.4 vs 17.1, P =.002), 5-HTP/TRP <0.89 (11.5 vs 17.6 months, P =.02), and 5-HT/TRP <5.78 (13.4 vs 19.1 months, P =.002) compared to patients with high levels. Shorter PFS in patients with 5-HT <78 ng/mL (P =.04), KYN <18 ng/mL (P =.02), 5-HT/TRP <5.78 (P =.001), KYN/TRP <2.55 (P =.005). Reduced KYN, 5-HTP, and 5-HT were independent predictors of poor OS. Conclusions: This study highlights an intriguing association between the degradation of TRP along the KP and SP and median survival times in GBM. Decreased KYN, 5-HTP, and 5-HT levels were associated with shorter OS.
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