Dataset Information

Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer

ABSTRACT: Gastric cancer (GC) is among the most aggressive malignancy affecting the world population. With almost a million cases remains in fifth position in incidence, while reaching the third position in mortality. The progression of GC is slow with several prolonged and sequential precancerous stages, including chronic gastritis, intestinal metaplasia, dysplasia and finally gastric cancer. Here we used the iTRAQ chemistry in combination with high-resolution mass spectrometry analysis to describe, from the proteomics point of view, the progression of the GC disease. Tissue samples from three stages: chronic gastritis, intestinal metaplasia and gastric adenocarcinoma, were selected for the quantitative proteomics analysis. From four independent replicates we identified and reported quantitative data for 3,914 different proteins with at least two unique peptides confidently quantified in all replicates. We uncovered pathways and processes dysregulated between the different stages. The initial transformation is characterized by the down-regulation of ribosomes and the protein processing in the endoplasmic reticulum, while overexpressing cell survival pathway and proteins such as GSTP1 and EPCAM. The transformation to GC involved the activation of DNA replication and Spliceosome pathways, overexpression of proteins supporting high rates of proliferation such as NPM1. In GC SIRT3 and SIRT5 were down-regulated, which correlated with the impairment of the mitochondrial pathways and overexpression of enzymes supporting the glycolytic phenotype such as HK3 and PCK2. Several proteins found dysregulated between stages of the progression of GC has potential to be used as specific biomarkers and/or targets for therapeutic treatment.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stomach

DISEASE(S): Stomach Cancer

SUBMITTER: Jeovanis Gil

LAB HEAD: Guadalupe Ayala Aguilar

PROVIDER: PXD008081 | Pride | 2019-09-27

REPOSITORIES: Pride

ACCESS DATA

Publications

Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer.

Fernández-Coto Diana Lashidua DL Gil Jeovanis J Hernández Angélica A Herrera-Goepfert Roberto R Castro-Romero Ivone I Hernández-Márquez Eva E Arenas-Linares Ana Silvia AS Calderon-Sosa Valia Tletzalli VT Sanchez-Aleman Miguel Ángel MÁ Mendez-Tenorio Alfonso A Encarnación-Guevara Sergio S Ayala Guadalupe G

Journal of proteomics 20180723

Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged and sequential precancerous stages including chronic gastritis, intestinal metaplasia, dysplasia, and finally gastric cancer. Here we used the iTRAQ approach combined with high-resolution mass spectrometry analysis to describe the spectrum of th ...[more]

PMID: 30048774

Similar Datasets

Project description:Helicobacter pylori is a well-recognized bacterium associated with the development of several histopathological lesions in the stomach. The chronic infection produces an inflammatory lesion known as gastritis. This lesion can later progress to more serious lesions such as intestinal metaplasia. Some attempts in the transcriptome of these conditions have been made; these however, have yielded limited information. Given the potential of high-throughput technologies for understanding biological processes altered and in the description of biomarkers of disease, we performed a genome-wide gene expression analysis in gastric biopsies. The aim of this study was to describe the altered molecular mechanism and potential biomarkers of follicular gastritis, chronic gastritis and intestinal metaplasia, through the identification of characteristic gene expression profiles in each histopathological lesion. The exploratory set comprised twenty-one biopsies from patients with follicular gastritis (n=7), chronic gastritis (n=7), and intestinal metaplasia (n=7), which were analyzed by whole-genome gene expression microarrays. The enrichment analyses and functional annotation of genes using computational tools were performed. The bioinformatics data of the same 21 biopsies were validated by real time PCR analysis while 79 FFPE samples were analyzed by immunohistochemistry. Gene expression analyses showed profiles for each histopathological lesion. Follicular gastritis had an expression profile with marked enrichment of immunologically-related genes. In contrast, chronic gastritis was characterized by a deregulation of mitochondrial-related genes and a down regulation of genes associated with protection against oxidative stress. Meanwhile, intestinal metaplasia showed an over expression of gastrointestinal stem cell markers and molecules related to RNA metabolism. Our results provide a comprehensive and reliable gene expression analysis of follicular gastritis, chronic gastritis and intestinal metaplasia disorders. The gene expression patterns described established a clear difference between the three pathologies studied and allowed the identification of several potential biomarkers for each histological change.

Dataset Information

Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer

Publications

Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure