TY - JOUR
T1 - Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer
AU - Fernández-Coto, Diana Lashidua
AU - Gil, Jeovanis
AU - Hernández, Angélica
AU - Herrera-Goepfert, Roberto
AU - Castro-Romero, Ivone
AU - Hernández-Márquez, Eva
AU - Arenas-Linares, Ana Silvia
AU - Calderon-Sosa, Valia Tletzalli
AU - Sanchez-Aleman, Miguel Ángel
AU - Mendez-Tenorio, Alfonso
AU - Encarnación-Guevara, Sergio
AU - Ayala, Guadalupe
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/8/30
Y1 - 2018/8/30
N2 - 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 the gastric cancer cascade. Biopsies from three stages: chronic gastritis, intestinal metaplasia, and gastric adenocarcinoma, were selected for analysis by quantitative proteomics. We identified and reported quantitative data for 3914 different proteins quantified with high confidence, uncovering pathways and processes dysregulated between the different stages. Intestinal metaplasia is characterized by the down-regulation of ribosomal proteins, with overexpression of cell survival proteins such as GSTP1 and EPCAM. The transformation to gastric cancer involves overexpression of the DNA replication and the spliceosome pathways. The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2. Several proteins found dysregulated during the progression of gastric cancer have potential to be used as specific biomarkers and/or therapeutic targets.
AB - 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 the gastric cancer cascade. Biopsies from three stages: chronic gastritis, intestinal metaplasia, and gastric adenocarcinoma, were selected for analysis by quantitative proteomics. We identified and reported quantitative data for 3914 different proteins quantified with high confidence, uncovering pathways and processes dysregulated between the different stages. Intestinal metaplasia is characterized by the down-regulation of ribosomal proteins, with overexpression of cell survival proteins such as GSTP1 and EPCAM. The transformation to gastric cancer involves overexpression of the DNA replication and the spliceosome pathways. The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2. Several proteins found dysregulated during the progression of gastric cancer have potential to be used as specific biomarkers and/or therapeutic targets.
KW - Cancer progression
KW - Chronic gastritis
KW - Gastric cancer
KW - Intestinal metaplasia
KW - Quantitative proteomics
KW - iTRAQ labelling
UR - http://www.scopus.com/inward/record.url?scp=85050392492&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2018.07.013
DO - 10.1016/j.jprot.2018.07.013
M3 - Artículo
C2 - 30048774
SN - 1874-3919
VL - 186
SP - 15
EP - 27
JO - Journal of Proteomics
JF - Journal of Proteomics
ER -