Longitudinal Circulating Nerve Growth Factor in Pancreatic Ductal Adenocarcinoma: An Exploratory Study of...

Nerve growth factor (NGF) signaling is involved in pancreatic ductal adenocarcinoma (PDAC) neurotropism, perineural invasion, pain, and tumor-stromal crosstalk, but its value as a circulating biomarker remains poorly defined. We retrospectively analyzed 51 patients with PDAC who underwent serial liquid-biopsy assessment across perioperative and advanced-disease timepoints. Circulating β-NGF was assessed in plasma, and samples without measurable NGF were classified as non-detectable. NGF was analyzed as both a zero-inflated continuous variable and a binary detectable/non-detectable biomarker. Phase-aligned associations with recurrence, disease-free survival, first-line progression-free survival, CA19-9, CEA, TGFβ, PD-L1, pain, and pathological perineural invasion were evaluated using non-parametric and permutation-based methods with false-discovery-rate adjustment. NGF availability was highest at first-line treatment initiation, where 9 of 40 patients had detectable NGF (22.5%). The clearest signal emerged postoperatively: patients who subsequently recurred had higher NGF values than those who did not (median 25.5 pg/mL vs. non-detectable; nominal p = 0.038). Detectable postoperative NGF was directionally associated with recurrence, while detectable NGF at first-line treatment initiation was associated with numerically shorter progression-free survival. Pooled active-disease measurements did not show a clear NGF increase versus postoperative samples, arguing against a generic disease-burden signal. No association remained significant after false-discovery-rate correction; therefore, all observed signals should be interpreted as exploratory and hypothesis-generating. These findings support prospective validation of circulating NGF within multimarker liquid-biopsy strategies focused on postoperative recurrence, perineural invasion-related biology, and treatment resistance in PDAC.