Abstract
Proteomics is a powerful approach to study the molecular mechanisms of cancer. In this study, we aim to characterize the proteomic profile of gastric cancer (GC) in patients with diabetes mellitus (DM) type 2. Forty GC tissue samples including 19 cases from diabetic patients and 21 cases from individuals without diabetes (control group) were selected for the proteomics analysis. Gastric tissues were processed following the single-pot, solid-phase-enhanced sample preparation approach—SP3 and enzymatic digestion with trypsin. The resulting peptides were analyzed by LC-MS Liquid Chromatography—Mass Spectrometry (LC-MS). The comparison of protein expression levels between GC samples from diabetic and non-diabetic patients was performed by label-free quantification (LFQ). A total of 6599 protein groups were identified in the 40 samples. Thirty-seven proteins were differentially expressed among the two groups, with 16 upregulated and 21 downregulated in the diabetic cohort. Statistical overrepresentation tests were considered for different annotation sets including the Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Disease functional databases. Upregulated proteins in the GC samples from diabetic patients were particularly enriched in respiratory electron transport and alcohol metabolic biological processes, while downregulated proteins were associated with epithelial cancers, intestinal diseases, and cell–cell junction cellular components. Taken together, these results support the data already obtained by previous studies that associate diabetes with metabolic disorders and diabetes-associated diseases, such as Alzheimer’s and Parkinson’s, and also provide valuable insights into seven GC-associated protein targets, claudin-3, polymeric immunoglobulin receptor protein, cadherin-17, villin-1, transglutaminase-2, desmoglein-2, and mucin-13, which warrant further investigation.
Highlights
IntroductionGastric cancer (GC) is the fifth most frequent cancer and the third leading cause of cancer deaths worldwide [1]
There were no significant differences in the clinicopathological features of the two groups, including gender, median age of diagnosis, tumor stage, and histological type (p > 0.05)
A schematic representation of the proteomics workflow performed in this study is depicted in Figure 51.of 14
Summary
Gastric cancer (GC) is the fifth most frequent cancer and the third leading cause of cancer deaths worldwide [1]. One of the most common risk factors is infection by Helicobacter pylori, a World Health Organization (WHO) class I carcinogen that is thought to be responsible for the majority of GCs [2]. Behavioral factors such as smoking, low fruit and vegetable intake, and high salt intake increase the risk of developing GC [2,3]. A complex interplay of several risk factors, including genetic susceptibility, microbial community, and dietary habits, contributes to create a prone environment for gastric carcinogenesis [2,4]
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