Impact of IGF2BP2 genetic variants and expression levels with the progression of endometrial cancer

Endometrial cancer (EC) is the most common gynecological cancer among women in high-income countries, and its intricate etiology involves a composite of genetic factors. Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) targets distinct types of RNA species to orchestrate tumor cell metabolism, invasion, and metastasis. Nevertheless, the impact of IGF2BP2 gene polymorphisms on the development of EC remains poorly understood. Here, to clarify the genetic association between IGF2BP2 and EC development, genotyping of three single-nucleotide polymorphisms (SNPs) of IGF2BP2 gene, including rs11705701, rs4402960, and rs1470579, were conducted in 190 patients and 295 cancer-free women. We found that none of these three loci was in association with the risk of developing EC. Further evaluation on their correlation with key clinicopathological features revealed that EC patients carrying at least one minor allele of rs1470579 (C) or rs4402960 (T) tend to develop cervical invasion more frequently than do those homozygous for the major allele. Analysis of omics data available in the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) indicated that genotypes of rs1470579 and rs4402960 are associated with elevated IGF2BP2 expression, and IGF2BP2 induction in tumors was linked to progression to advanced disease and poor survival in patients with uterine corpus endometrial carcinoma. These results suggest that alterations in IGF2BP2 levels attributed by genetic variants may influence EC aggressiveness.