Differential proteomic analysis of noncardia gastric cancer from individuals of northern Brazil.

Mariana Ferreira Leal,Rommel Rodríguez Burbano,Paulo Pimentel Assumpção,Roger Chammas,Marília De Arruda Cardoso Smith,Danielle Queiroz Calcagno,Samia Demachki,Ismael Dale Cotrim Guerreiro Da Silva,Janete Chung,Jörg D Hoheisel

doi:10.1371/journal.pone.0042255

Mariana Ferreira Leal, Rommel Rodríguez Burbano + Show 8 more

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https://doi.org/10.1371/journal.pone.0042255

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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.

Highlights

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1]
Proteomic analysis of gastric tissue We analyzed the proteome of 15 noncardia GC samples – 6 without lymph node metastasis and 9 with lymph node metastasis – and 15 matched control tissues (Table 1)
Our differential proteomic analysis revealed several potential proteins that are deregulated in noncardia GC of individuals from Northern Brazil

Summary

Introduction

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1]. The overall relative 5-year survival rate is currently less than 20% [2]. In Northern Brazil, GC is the second most frequent neoplasia among males and the third in females [3]. In Para State, Northern Brazil, the 5-year survival rate is about 9–10% [4]. The incidence rates of cardia GC are relatively high in the professional classes [6]. Over the last few decades, the incidence of noncardia GC has substantially declined in developed regions of the world. This subtype still constitutes the majority of GC cases worldwide and remains common in many geographic regions, including China, Japan, Eastern Europe and Central/South Americas [8]. The understanding of GC biology and the identification of cancer biomarkers are necessary to reduce the mortality rates through cancer screenings in high-risk populations, to increase early diagnosis, and to develop new target therapies

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