Comparing intestinal versus diffuse gastric cancer using a PEFF-oriented proteomic pipeline.

Autor: Wippel HH; Computational Mass Spectrometry & Proteomics Group, Carlos Chagas Institute, Fiocruz - Paraná, Brazil., Santos MDM; Computational Mass Spectrometry & Proteomics Group, Carlos Chagas Institute, Fiocruz - Paraná, Brazil., Clasen MA; Computational Mass Spectrometry & Proteomics Group, Carlos Chagas Institute, Fiocruz - Paraná, Brazil., Kurt LU; Computational Mass Spectrometry & Proteomics Group, Carlos Chagas Institute, Fiocruz - Paraná, Brazil., Nogueira FCS; Laboratory of Proteomics, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Protein Chemistry, Proteomic Unit, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Carvalho CE; Pathology Service of the Clementino Fraga Filho University Hospital (HUCFF-UFRJ), Rio de Janeiro, Brazil., McCormick TM; Departament of Pathology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Neto GPB; Division of Esophageal and Gastric Surgery, General Surgery Service of the HUCFF-UFRJ, Rio de Janeiro, Brazil., Alves LR; Laboratory of Gene Expression Regulation, Carlos Chagas Institute, Fiocruz - Paraná, Brazil., da Gloria da Costa Carvalho M; Departament of Pathology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Carvalho PC; Computational Mass Spectrometry & Proteomics Group, Carlos Chagas Institute, Fiocruz - Paraná, Brazil. Electronic address: paulo@pcarvalho.com., Fischer JSDG; Computational Mass Spectrometry & Proteomics Group, Carlos Chagas Institute, Fiocruz - Paraná, Brazil. Electronic address: julifr@gmail.com.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2018 Jan 16; Vol. 171, pp. 63-72. Date of Electronic Publication: 2017 Oct 12.
DOI: 10.1016/j.jprot.2017.10.005
Abstrakt: Gastric cancer is the fifth most common malignant neoplasia and the third leading cause of cancer death worldwide. Mac-Cormick et al. recently showed the importance of considering the anatomical region of the tumor in proteomic gastric cancer studies; more differences were found between distinct anatomical regions than when comparing healthy versus diseased tissue. Thus, failing to consider the anatomical region could lead to differential proteins that are not disease specific. With this as motivation, we compared the proteomic profiles of intestinal and diffuse adenocarcinoma from the same anatomical region, the corpus. To achieve this, we used isobaric labeling (iTRAQ) of peptides, a 10-step HILIC fractionation, and reversed-phase nano-chromatography coupled online with a Q-Exactive Plus mass spectrometer. We updated PatternLab to take advantage of the new Comet-PEFF search engine that enables identifying post-translational modifications and mutations included in neXtProt's PSI Extended FASTA Format (PEFF) metadata. Our pipeline then uses a text-mining tool that automatically extracts PubMed IDs from the proteomic result metadata and drills down keywords from manuscripts related with the biological processes at hand. Our results disclose important proteins such as apolipoprotein B-100, S100 and 14-3-3 proteins, among many others, highlighting the different pathways enriched by each cancer type.
Significance: Gastric cancer is a heterogeneous and multifactorial disease responsible for a significant number of deaths every year. Despite the constant improvement of surgical techniques and multimodal treatments, survival rates are low, mostly due to limited diagnostic techniques and late symptoms. Intestinal and diffuse types of gastric cancer have distinct clinical and pathological characteristics; yet little is known about the molecular mechanisms regulating these two types of gastric tumors. Here we compared the proteomic profile of diffuse and intestinal types of gastric cancer from the same anatomical location, the corpus, from four male patients. This methodological design aimed to eliminate proteomic variations resulting from comparison of tumors from distinct anatomical regions. Our PEFF-tailored proteomic pipeline significantly increased the identifications as when compared to previous versions of PatternLab.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE