{
  "abstract": "Background/Objectives: Neural–tumor interactions are increasingly recognized in gastric cancer (GC), yet their relationship with circulating neuroactive mediators remains incompletely understood. This systematic review aimed to synthesize human evidence on circulating neurotransmitters, neuropeptides, and related mediators, assess their diagnostic, clinicopathological, treatment-associated, and prognostic relevance, and integrate clinical findings within a translational framework of neuro–tumor signaling. Methods: PubMed/MEDLINE, Scopus, and Web of Science Core Collection were systematically searched following PRISMA 2020 guidelines. Eligible studies assessed circulating neuroactive mediators in patients with GC. Clinical findings were synthesized by evidence domain and contextualized using complementary tumor-level receptor and signaling evidence. Results: Twenty-four publications representing 23 independent cohorts were included. Replicated circulating alterations were identified for galanin, motilin, and cholecystokinin, although gastrointestinal physiology and treatment-related changes complicated their interpretation. Progastrin-releasing peptide demonstrated diagnostic discrimination in a single study (AUC 0.713; sensitivity 85.9%; specificity 81.2%) and associations with clinicopathological characteristics. Dopaminergic and catecholamine-related alterations suggested systemic neuroendocrine involvement, while higher normetanephrine was associated with poorer survival in univariable analysis. Complementary mechanistic evidence implicated serotonergic, substance P/NK-1R, and neurotensin/NTSR1 pathways in tumor-associated signaling. The translational evidence map highlighted three overlapping biological dimensions: tumor-associated receptor-mediated signaling, systemic neuroendocrine and stress adaptations, and gastrointestinal physiological responses. However, small cohorts, heterogeneous biological matrices, historical assay variability, and limited independent validation restricted clinical interpretation. Conclusions: Circulating neuroactive mediators represent a biologically plausible but insufficiently validated biomarker domain in GC. Their clinical translation requires standardized prospective studies integrating circulating measurements with matched tumor biology, clinically relevant comparator populations, longitudinal outcomes, and independent validation. Pathway-oriented multimarker approaches may ultimately provide more informative neuroactive signatures than individual mediators.",
  "abstract_shown": true,
  "affiliations": [
    "Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania",
    "Department of Occupational Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania",
    "Department of Immunology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania",
    "Research Center of Periodontal-Systemic Interactions, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania",
    "Department of Neurology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania",
    "Department of Microbiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania",
    "Department 10—General Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania",
    "Department of Surgical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bogdan Cristian Albu"
    },
    {
      "affs": [
        1
      ],
      "name": "Ancuța-Ramona Camen"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Mihail Virgil Boldeanu",
      "orcid": "0000-0003-2481-6138"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Mohamed-Zakaria Assani",
      "orcid": "0009-0009-3146-8769"
    },
    {
      "affs": [
        4
      ],
      "name": "Carmen Valeria Albu",
      "orcid": "0009-0008-9603-5860"
    },
    {
      "affs": [
        5
      ],
      "name": "Lidia Boldeanu",
      "orcid": "0000-0002-4817-1365"
    },
    {
      "affs": [
        4
      ],
      "name": "Elena Albu"
    },
    {
      "affs": [
        6
      ],
      "name": "Dragos Ene"
    },
    {
      "affs": [
        7
      ],
      "name": "Mihai Călin Ciorbagiu"
    },
    {
      "affs": [
        7
      ],
      "name": "Emil Moraru"
    },
    {
      "affs": [
        7
      ],
      "name": "Cecil Sorin Mirea"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/78ggx0wpak0g3.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18213562",
  "fulltext_url": null,
  "id": "78ggx0wpak0g3",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/21/3562",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/78ggx0wpak0g3.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:21Z",
      "native_id": "10.3390/cancers18213562",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/21/3562"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6694",
      "subfield": "oncology"
    }
  ],
  "title": "Circulating Neurotransmitters, Neuropeptides, and Neuroactive Mediators in Gastric Cancer: A Systematic Review of Diagnostic, Prognostic, and Clinicopathological Evidence",
  "title_text": "Circulating Neurotransmitters, Neuropeptides, and Neuroactive Mediators in Gastric Cancer: A Systematic Review of Diagnostic, Prognostic, and Clinicopathological Evidence",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:23:01Z",
  "url": "https://research.draconitic.com/paper/78ggx0wpak0g3",
  "venue": "Cancers",
  "versions": []
}