Differential Proteomic Analysis of Noncardia Gastric Cancer from Individuals of Northern Brazil

Abstract

Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in larger clinical study sets.

Prohibitin Expression Deregulation in Gastric Cancer Is Associated with the 3′ Untranslated Region 1630 C>T Polymorphism and Copy Number Variation

“…It has been suggested that loss of mitochondrial PHB expression (cytoplasmic localization, as observed in our samples) could lead to accelerated proteolysis of membrane proteins and impair function of the mitochondrial respiratory chain [10]. Our previous proteomic study showed that several proteins involved in energy metabolism pathways (mitochondrial dysfunction, pyruvate metabolism, oxidative phosphorylation, citrate circle, glycolysis/gluconeogenesis) were deregulated [31] and suggested that prominent mitochondrial functions may be altered, shifting energy production in GC cells and suggesting the Warburg effect [32].…”

Discovery of gastric cancer specific biomarkers by the application of serum proteomics

“…HSPs are responsible for many cytoprotective mechanisms to stress conditions . HSP27 , HSP60, HSP70 , HSP90, and HSP 105 were observed in previous studies. Other proteins as enolase‐alpha (ENOA), annexin (ANXA) , transgelin (TGLN) , carbon anhydrase 2 (CA2) have been reported in several gastric cancer proteomic studies.…”

Two‐dimensional gel electrophoresis of gastric tissue in an alkaline pH range

“…Of the proteins with decreased abundance, some have already been reported to be associated with GA, such as ADH1C , HADH , IDH2 , and IGHG1 . AIFM1 was found decreased in our case, although it has been reported as increased in the literature , as also seen for HADH .…”