LGALS4 – Colorectal Cancer

LGALS4, encoding galectin‑4, has emerged as a gene of interest in colorectal cancer, with several independent lines of evidence supporting its role in tumorigenesis. Recent multi‑patient studies have revealed that specific promoter single nucleotide polymorphisms (SNPs) in LGALS4, namely rs116896264 and rs73933062, form a distinct haplotype that correlates with increased gene expression in colorectal cancer samples (PMID:26681582).

In a cohort of 75 colorectal cancer patients, the co‑occurrence of these SNPs was observed in 21% of cases (PMID:26681582), suggesting a regulatory mechanism that leads to gene overexpression. The study utilized quantitative RT‑PCR, luciferase reporter, and pull‑down assays to confirm that these promoter variants significantly alter transcription factor binding sites, thereby modifying LGALS4 expression levels.

Additional evidence from a multi‑gene assessment study, which included LGALS4 among a panel of candidates associated with colorectal malignancies, further supports its potential clinical relevance. This study, employing large datasets from TCGA and GEO, underscores a consistent pattern of differential gene expression in colorectal tumors and highlights LGALS4 as a candidate for diagnostic and prognostic evaluation (PMID:38988920).

The genetic evidence for LGALS4’s involvement in colorectal cancer is bolstered by the consistent identification of promoter variants that impact gene regulation. Although a formal familial segregation analysis has not been reported, the observed frequency of these variants in sporadic cancer cases adds weight to the association. The evidence points to a regulatory disruption rather than classic coding mutations, emphasizing a mechanism based on altered transcriptional modulation.

Functionally, the experimental assays have demonstrated that the presence of these SNPs directly influences transcription factor binding and promoter activity. Luciferase reporter assays and pull‑down experiments have provided a mechanistic link between the genetic variants and elevated LGALS4 expression, offering strong functional evidence in support of a pathogenic role in colorectal cancer.

In conclusion, the convergence of genetic association data and robust functional studies underlines a strong link between LGALS4 dysregulation and colorectal cancer. This integrated evidence highlights LGALS4 as a promising biomarker for diagnostic decision‑making and a potential therapeutic target. Key take‑home message: LGALS4 represents a viable molecular target for enhancing colorectal cancer clinical management.

References

• Mutagenesis • 2016 • Promoter SNPs rs116896264 and rs73933062 form a distinct haplotype and are associated with galectin‑4 overexpression in colorectal cancer PMID:26681582
• Translational Cancer Research • 2024 • Value analysis of ITLN1 in the diagnostic and prognostic assessment of colorectal cancer PMID:38988920

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