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Causal Relationship Between Galectins With Neuroblastoma: A Mendelian Randomization Study.

Chunxi Long^1,2, Ping Liang^1,2, Xiaoqin Liu^1,2

¹Department of Neurosurgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, P.R. China.

Molecular Neurobiology

|November 22, 2025

Summary

Galectin-9 (Gal-9) may causally increase neuroblastoma (NB) risk, unlike Gal-1 and Gal-3. This Mendelian randomization study suggests Gal-9 as a potential factor in NB development.

Keywords:

Causality Galectins Instrumental variable Mendelian randomization Neuroblastoma

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Area of Science:

Oncology
Genetics
Biochemistry

Background:

Galectins are proteins implicated in cancer progression, including tumor growth and metastasis.
Neuroblastoma (NB) risk is potentially linked to galectins, but causal associations remain unclear.
Galectins are classified into prototype (Gal-1), chimera (Gal-3), and tandem repeat (Gal-9) types.

Purpose of the Study:

To investigate the causal effect of galectins (Gal-1, Gal-3, Gal-9) on neuroblastoma (NB) risk.
To clarify the role of specific galectins in the etiology of NB.
To utilize Mendelian randomization (MR) for assessing genetic predisposition to NB risk.

Main Methods:

A two-sample Mendelian randomization (MR) study design was employed.
Genome-wide association study (GWAS) summary statistics were used to identify single-nucleotide polymorphisms (SNPs) as instrumental variables for Gal-1, Gal-3, and Gal-9.
Inverse-variance weighted (IVW) method was the primary analysis, supplemented by MR-robust adjusted profile score (MR-RAPS), weighted median, and other methods.

Main Results:

Genetically predicted Galectin-9 (Gal-9) levels were associated with an increased risk of neuroblastoma (NB) (OR=1.639, P=0.004).
No significant causal association was found between Gal-1 or Gal-3 and NB risk.
Sensitivity analyses, including MR Steiger and leave-one-out tests, confirmed the robustness and reliability of the findings for Gal-9.

Conclusions:

Galectin-9 (Gal-9) shows a potential causal association with an increased risk of neuroblastoma (NB).
Gal-1 and Gal-3 do not appear to have a significant causal effect on NB risk.
These findings provide insights into the role of Gal-9 in NB development and may inform future therapeutic strategies.