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巴西北部非贲门胃癌的差异蛋白质组学分析。

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

机构信息

Genetics Division, Department of Morphology and Genetic, Federal University of São Paulo, São Paulo, Brazil.

出版信息

PLoS One. 2012;7(7):e42255. doi: 10.1371/journal.pone.0042255. Epub 2012 Jul 30.

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.

摘要

胃癌是全球癌症相关死亡的第二大主要原因。通过开发新的筛查检测和早期诊断方法以及新的靶向治疗方法,有必要鉴定新的癌症生物标志物来降低死亡率。在这项研究中,我们对来自巴西北部的非贲门胃肿瘤患者进行了蛋白质组学分析。通过二维电泳和质谱对蛋白质进行分析。为了鉴定差异表达的蛋白质,我们使用具有自举重采样的统计检验来控制多重比较分析中的 I 型错误。我们鉴定出 111 种参与胃癌发生的蛋白质。计算分析揭示了几种参与能量产生过程的蛋白质,并强化了胃癌中的沃伯格效应。进一步评估了 ENO1 和 HSPB1 的表达。选择 ENO1 是因为它在有氧糖酵解中的作用,可能有助于沃伯格效应。尽管我们在蛋白质组学分析中观察到 ENO1 的两个上调斑点,但 Western blot 显示ENO1 在胃肿瘤中的平均表达降低。然而,在更具侵袭性的肿瘤中,平均 ENO1 表达似乎增加。蛋白质组学和 Western blot 分析之间缺乏相关性可能是由于存在其他 ENO1 斑点,这些斑点的表达略有降低,但对蛋白质的平均表达有很大影响。在肿瘤中,HSPB1 被细胞应激诱导以保护细胞免受凋亡。在本研究中,HSPB1 在一组胃癌样本中表现出蛋白和 mRNA 表达升高。然而,HSPB1 表达与临床病理特征之间没有观察到相关性。在这里,我们鉴定了来自巴西北部个体的几种可能的胃癌生物标志物。如果在更大的临床研究中得到验证,这些生物标志物可能有助于评估预后和分层治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4302/3408468/8a19df6617c2/pone.0042255.g001.jpg

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