Evidence map›Paper›PMID 40595538›Full record

ArticleNature communications2025

Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI.

Abhishek Tyagi, Shih-Ying Wu, Jee-Won Kim, Ravindra Pramod Deshpande, Kerui Wu, Eleanor C Smith, Giuseppe L Banna, Kounosuke Watabe

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Abhishek TyagiDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.ORCID http://orcid.org/0000-0002-0155-2099
Shih-Ying WuDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Jee-Won KimDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Ravindra Pramod DeshpandeDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.ORCID http://orcid.org/0000-0002-4634-9967
Kerui WuNanoscience Department, Joint School of Nanoscience & Nanoengineering, Greensboro, NC, 27401, USA.ORCID http://orcid.org/0000-0002-5504-8875
Eleanor C SmithDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Giuseppe L BannaPortsmouth Hospitals University NHS Trust, Faculty of Science and Health, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.ORCID http://orcid.org/0000-0003-0764-3650
Kounosuke WatabeDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA. kwatabe@wakehealth.edu.ORCID http://orcid.org/0000-0001-7441-6322

Funding

Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4M
Roles of long-non-coding RNA, XIST, in brain metastasis of breast cancerR01CA205067 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WATABE, KOUNOSUKE · 2017 to 2021
$2.2M
NCI NIH HHS P30 CA012197NCI NIH HHS R01 CA205067U.S. Department of Defense (United States Department of Defense) HT9425-24-1-0144U.S. Department of Defense (United States Department of Defense) W81XWH2110075U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA205067
6 · The paper itself

Abstract

Obesity is a known risk factor for many cancers, yet recent studies reveal a paradoxical association between low body mass index (BMI) and increased brain metastasis in lung cancer-referred to as the "obesity paradox," with unclear molecular mechanism(s). Here, we show a significantly higher incidence of brain metastasis in low-BMI lung cancer patients compared to those with high-BMI or other cancer brain metastasis in a pan-analysis of 7628 patients. Mechanistically, low BMI activates ghrelin-GHSR signaling, increasing neuronal neuropeptide Y (NPY) secretion, which promotes tumor metabolic reprogramming via NPY-Y5R, facilitating brain colonization. Elevated plasma ghrelin levels in cancer-free low-BMI subjects suggest its potential as a prognostic biomarker for predicting brain metastasis. Notably, targeting NPY-Y5R or reversing low BMI effectively suppresses brain metastasis, supporting its pro-metastatic role. These findings provide a strong rationale for developing targeted interventions to treat or prevent brain metastasis in lung cancer patients with low BMI.

Indexed as

Brain NeoplasmsGhrelinLung NeoplasmsNeuronsNeuropeptide YAgedAnimalsBody Mass IndexCell Line, TumorFemaleHumansMaleMiceMiddle AgedObesityReceptors, GhrelinGhrelinNeuropeptide YReceptors, GhrelinReceptors, Neuropeptide Y

Identifiers

PMID40595538
PMCPMC12218320

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.