J Gastric Cancer.  2022 Oct;22(4):348-368. 10.5230/jgc.2022.22.e31.

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

• Dominkuš PP
• Mesic A
• Hudler P

• KMID: 2535112
• DOI: http://doi.org/10.5230/jgc.2022.22.e31

Abstract

Purpose
Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features.
Materials and Methods
The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay.
Results
The PLK2 C _rs15009 -C _rs963615 haplotype was under-represented in the GC group compared to that in the control group (P _corr =0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM T _rs228589 -A _rs189037 -G _rs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC.
Conclusions
PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

Keyword

Gastric cancer; Genetic variation; Chromosomal instability; Cell cycle genes; MiR-23b-5p