Proteomic Analysis of Endometrial Cancer Tissues from Patients with Type 2 Diabetes Mellitus

Life

Assim A. Alfadda¹  Maria Arafah²  Anas M. Abdel Rahman³  Khalid Akkour⁴  Hani Alhalal⁴  Afshan Masood⁵  Hicham Benabdelkamel⁵  Mohthash Musambil⁵  Mohamed Rafiullah⁶  Ibrahim O. Alanazi⁷  Muhammad Mujammami⁸ 

[1] Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia;Department of Pathology, College of Medicine, King Saud University, King Saud University Medical City, Riyadh 11461, Saudi Arabia;Metabolomics Section, Center for Genome Medicine, Department of Clinical Genomics, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia;Obstetrics and Gynecology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia;Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia;Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia;The National Center for Biotechnology (NCB), Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia;University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh 11461, Saudi Arabia;

关键词: uterus;    endometrial cancer;    diabetes;    tissue;    proteomics;    2D-DIGE;   

DOI  :  10.3390/life12040491

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown