Longitudinal Circulating Nerve Growth Factor in Pancreatic Ductal Adenocarcinoma: An Exploratory Study of Postoperative Recurrence and First-Line Disease Control
4 affiliations
- 1Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy
- 2Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
- 3Lab Medical Oncology, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands
- 4Cancer Pharmacology Lab, AIRC Start-Up Unit, Fondazione Pisana per la Scienza, 56126 Pisa, Italy
Abstract
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.
Related
- An intron retention-derived secreted Endoglin Isoform as a circulating biomarker in pancreatic ductal adenocarcinoma.
- Longitudinal Drain-Fluid Proteomics Reveals Procedure-Specific Signatures of Postoperative Leakage after Pancreatic and Colorectal Surgery
- Prognostic Value and Longitudinal Dynamics of Multigene Circulating Tumor DNA in Advanced Pancreatic Cancer Treated with 5-Fluorouracil-Based Chemotherapy.
- Novel self-assembling peptide gel CK2-085-SP (SPG-178) as a sealant for preventing postoperative pancreatic fistula after pancreatic resection: a study protocol for a prospective, exploratory, investigator-initiated clinical trial (PepSeal-001).
- Benchmarking the Intratumoral Microbiome in Pancreatic Ductal Adenocarcinoma: A Longitudinal Assessment of Contamination Sources and Decontamination Strategies
BibTeX
@article{garajova2026longitudinal,
title = {{Longitudinal Circulating Nerve Growth Factor in Pancreatic Ductal Adenocarcinoma: An Exploratory Study of Postoperative Recurrence and First-Line Disease Control}},
author = {Ingrid Garajová and Graziana Digiacomo and Andrea Cavazzoni and Bing Wang and Michela Verze and Roberta Minari and Virginia Agnetti and Elisa Giovannetti},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101433},
url = {https://www.mdpi.com/2218-273X/16/10/1433},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Longitudinal Circulating Nerve Growth Factor in Pancreatic Ductal Adenocarcinoma: An Exploratory Study of Postoperative Recurrence and First-Line Disease Control
AU - Ingrid Garajová
AU - Graziana Digiacomo
AU - Andrea Cavazzoni
AU - Bing Wang
AU - Michela Verze
AU - Roberta Minari
AU - Virginia Agnetti
AU - Elisa Giovannetti
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101433
UR - https://www.mdpi.com/2218-273X/16/10/1433
AB - 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.
SN - 2218-273X
ER -