High plasma histidine concentration predicts a favorable prognosis in patients with ampullary cancer

Circulating amino acid levels differ between patients with cancer and healthy individuals, and plasma histidine levels are lower in patients with periampullary cancer. This study examines histidine-related metabolic signaling in ampullary cancer. In total, 106 cancer specimens and 49 plasma samples from ampullary cancer patients were analyzed using immunohistochemistry, high-performance liquid chromatography for histidine levels, and enzyme-linked immunosorbent assays for histamine levels. Additionally, three ampullary cancer cell lines (TGBC-18 TKB, SNU-478, and SNU-869) were treated with histidine or histamine to assess growth. Plasma histidine levels were lower in patients with ampullary cancer than in healthy controls, whereas plasma histamine levels were similar between these groups. Elevated plasma histidine level was correlated with improved recurrence-free and overall survival in patients with ampullary cancer, as demonstrated by Kaplan-Meier survival analysis and multivariate Cox proportional hazards modeling. Expression of histidine-catabolic enzymes, namely histidine decarboxylase and histidine ammonia-lyase, was synergistic and positively correlated with early-stage cancer. Histidine treatment suppressed cancer cell proliferation, whereas histamine promoted cell proliferation of TGBC-18 TKB ampullary cancer cells. These findings suggest that plasma histidine is a prognostic survival factor, and combined treatment with histidine may offer therapeutic potential in patients with ampullary cancer.