Assessing Urinary Para-Hydroxyphenylacetic Acid as a Biomarker Candidate in Neuroendocrine Neoplasms

The management of neuroendocrine neoplasms (NENs) involves the measurement of serum chromogranin A (s-CGA), serum neuro-specific enolase (s-NSE), and urinary 5-hydroxindolacetic acid (5-HIAA). Urinary para-hydroxyphenylacetic acid (u-pHPAA), a metabolite of tyrosine, has been proposed as a potential biomarker for these diseases. This study aims to evaluate the effectiveness of u-pHPAA and tyrosine as biomarkers. We measured the levels of s-CgA, s-NSE, u-5-HIAA, u-pHPAA, and tyrosine in blood or 24 h urine samples collected at baseline (T₀) and after 1 year of follow-up (T₁) from a limited cohort of patients enrolled at Istituto Nazionale Tumori-IRCCS-Fondazione "G. Pascale". Biomarker values were normalized using the ratios between T₁ and T₀ values (T₁/T₀ parameters). The T₁/T₀ ratios for s-CgA and u-pHPAA were significantly associated with the outcome of death (p = 0.044 and p = 0.022, respectively). An ROC curve analysis demonstrated outstanding performances for these biomarkers (AUC = 0.958 and AUC = 1.00, respectively) and the Kaplan-Meier survival analysis showed significant Log-rank test results (p = 0.001 and p < 0.001, respectively). Additionally, T₀ serum tyrosine correlated with the outcome of death (p = 0.044), with the ROC curve showing good performance (AUC = 0.958) and the Kaplan-Meier analysis yielding significant Log-rank test results (p = 0.007). Our study confirms the role of s-CgA in the management of NEN patients and highlights the potential roles of u-pHPAA and serum tyrosine as biomarkers. Further research is needed to validate our findings in larger populations.