Endometrial cancer (EC) is the most common form of gynecological
cancer.
Type 2 diabetes mellitus is associated with an increased risk of EC. Currently, no proteomic studies have investigated the role of diabetes in
endometrial cancers from clinical samples. The present study aims to elucidate the molecular link between diabetes and EC using a proteomic approach. Endometrial tissue samples were obtained from age-matched patients (EC Diabetic and EC Non-Diabetic) during surgery. Untargeted proteomic analysis of the endometrial tissues was carried out using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted
laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF). A total of 53
proteins were identified, with a significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two groups, among which 30 were upregulated and 23 downregulated in the EC Diabetic group compared to EC Non-Diabetic. The significantly upregulated
proteins included peroxiredoxin-1,
vinculin,
endoplasmin,
annexin A5,
calreticulin, and
serotransferrin. The significantly downregulated
proteins were
myosin regulatory light
polypeptide 9,
Retinol dehydrogenase 12,
protein WWC3, intraflagellar
transport protein 88 homolog,
superoxide dismutase [Cu-Zn], and
retinal dehydrogenase 1. The network pathway was related to connective tissue disorder, developmental disorder, and hereditary disorder, with the identified
proteins centered around dysregulation of ERK1/2 and
F Actin signaling pathways.
Cancer-associated
protein alterations such as upregulation of peroxiredoxin-1,
annexin 5, and iNOS, and downregulation of RDH12,
retinaldehyde dehydrogenase 1, SOD1, and MYL 9, were found in the EC tissues of the diabetic group. Differential expression of
proteins linked to
cancer metastasis, such as the upregulation of
vinculin and
endoplasmin and downregulation of WWC3 and IFT88, was seen in the patients with diabetes.
Calreticulin and
alpha-enolase, which might have a role in the interplay between diabetes and EC, need further investigation.