PLK2 Single Nucleotide Variant in Gastric Cancer Patients Affects miR-23b-5p Binding

Area of Science:

• Genetics and Genomics
• Cancer Biology
• Molecular Oncology

Background:

• Chromosomal instability is a key characteristic of gastric cancer (GC).
• Single nucleotide variants (SNVs) in cell cycle genes can drive this instability.
• Investigating specific gene SNVs may reveal insights into GC development and progression.

Purpose of the Study:

• To examine the association between SNVs in PLK2, PLK3, and ATM genes and the risk of developing GC.
• To explore the relationship between these SNVs and various clinicopathological features of GC.
• To investigate the role of miR-23b-5p in GC pathogenesis and prognosis.

Main Methods:

• A genotyping study involving 542 GC patients and healthy controls.
• Generalized linear models for risk and clinicopathological association analyses.
• Kaplan-Meier survival analysis and luciferase reporter assays for microRNA binding analysis.

Main Results:

• Specific PLK2 haplotypes and genotypes showed differential associations with GC risk in males and females.
• PLK3 and ATM SNVs were linked to altered GC risk and the absence of specific invasive features (vascular and perineural invasion).
• miR-23b-5p was found to bind to PLK2 rs15009, and low miR-23b expression correlated with longer patient survival.

Conclusions:

• SNVs in PLK2, PLK3, and ATM may serve as predictive markers for GC risk and clinicopathological outcomes.
• PLK2 rs15009 influences miR-23b-5p binding, highlighting a novel molecular mechanism.
• MiR-23b-5p expression levels show prognostic potential for survival in GC patients.