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

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.

SUBMITTER: Leal MF

PROVIDER: S-EPMC3408468 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Leal Mariana Ferreira MF Chung Janete J Calcagno Danielle Queiroz DQ Assumpção Paulo Pimentel PP Demachki Samia S da Silva Ismael Dale Cotrim Guerreiro ID Chammas Roger R Burbano Rommel Rodríguez RR de Arruda Cardoso Smith Marília M

PloS one 20120730 7

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 diff ...[more]

PMID: 22860099

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Project description:Purpose: In carcinogenesis, the stomach, the MYC gene is frequently amplified and its protein is overexpressed, which contributes to uncontrolled cell proliferation mucosal gástrica.Três cell lines were subjected to sequencing semiconductor Proton Ion before and after the silencing of MYC. These lines were originating from diffuse and intestinal histologic types and the third of a metastasis from a stomach tumor originating in a ascites. Methods: mRNA profiles were generated from three established lines of CG previously characterized by our group. AGP01 (Obtained from ascitic fluid of an intestinal-type GC), ACP02 (diffuse-type GC) and ACP03 (intestinal-type GC). The three cell lines present chromosome 8 trisomy and MYC amplification, reflecting the genetic characteristics found in gastric cancer samples from Northern Brazil. They were generated by sequencing depth in triplicate using the Sequencer ™ Ion Proton. Raw data reads Obtained by primary sequencing Were Submitted to quality control in order to calculate alignment and to assess how the reads behave When Compared to the reference human genome (Hg19 / GRCh37). The aligned reads Were mapped and quantified using TMAP. Gene expression levels Were quantified using Sailfish pack software and the RPKM (Reads Per kilobase per Million mapped reads) method was used to estimate Then expression levels gene. Results: Using analysis of an optimized workflow, we mapped more than 13 million readings sequences between our samples from the human genome. Were mapped a total of 917 up-regulated genes and 1,566 different genes down-regulated Were When comparing the expression of AGP01 non-targeting control (1C) versus AGP01 MYC-silenced (1M), with a total of 2,483 DEGS. The evaluation of ACP02 cells treated with non-targeting control (2C) versus ACP02 MYC-silenced (2M) Showed a total of 5,327 DEGS, with 1,299 up-regulated and 4,098 down-regulated genes. The total of 4,117 were found DEGS When comparing ACP03 control cells (3C) with ACP03 MYC-silenced cells, with 3,274 up-regulated and 843 down-regulated genes. Silencing of the MYC gene, allowed the detection of more than 1,000 DEGS (Differentially Expressed Genes) between the three strains that were considered significant if the False Discovery Rate (FDR) was ≤0.001, P-value <0.05, and the absolute value of the Fold change (FC) was ≥1. The analysis of DEGS showed 22% and 34% were detected with a profile down-regulated in intestinal and diffuse type, respectively. The up-regulated profile was higher in the intestinal type, with 77% of DEGS than the diffuse type with 13% DEGS. Furthermore, the lineage from metastasis showed 33% of DEGS up-regulated and 66% of DEGS down-regulated. Conclusions: Our study is the first to describe bioinformatics methods the effect before and after the silencing of the MYC gene in cell lines of gastric cancer northern people of Brazil. Our results showed that depending on the histological type there are many functional genes between the three strains that were recorded significantly associated with pathways enriched for cancer, metabolism, adhesion, cell cycle, proteolysis and signaling, suggesting the existence of routes of different carcinogenesis that lead normal mucosa to turn into gastric cancer.

Project description:Increasing noncardia gastric cancer incidence rates among individuals age younger than 50 years have gained much attention, particularly as causes remain unknown. Using population-based NIH/NCI's Surveillance, Epidemiology, and End Results (SEER) program data from 2007 to 2015, multivariable logistic regression was used to quantify associations between race/ethnicity and clinicodemographic features among young-onset noncardia gastric cancer patients. A total of 2,872 individuals ages 20 to 49 years were diagnosed with primary noncardia gastric cancer. Age at diagnosis, insurance status, anatomic subsite, American Joint Committee on Cancer (AJCC) clinical stage, histologic type, tumor grade, surgery, and county-level smoking prevalence differed by race/ethnicity (all P ? 0.003). Compared with non-Hispanic whites, Hispanics were more likely to be diagnosed at younger ages [odds ratio (OR) = 0.97; 95% confidence intervals (CI), 0.95-0.99], on Medicaid/uninsured (OR = 3.83; 95% CI, 2.89-5.08), diagnosed with higher grade tumors (OR = 1.93; 95% CI, 1.32-2.84), and less likely to undergo surgery (OR = 0.62; 95% CI, 0.44-0.88) or to reside in counties with higher smoking prevalence (OR = 0.15; 95% CI, 0.11-0.21) after adjustment for sex, subsite, and histologic type. Asian/Pacific Islanders were more likely to be female (OR = 1.40; 95% CI, 1.04-1.88), and less likely to be diagnosed with metastatic disease (OR = 0.59; 95% CI, 0.37-0.95) or to reside in counties with higher smoking prevalence (OR = 0.13; 95% CI, 0.08-0.19). Approximately two in every five patients with young-onset noncardia gastric cancer are Hispanic. Further investigation into the molecular heterogeneity of young-onset noncardia gastric cancers by race/ethnicity to understand etiologies underlying this rising disease epidemic is warranted. This population-based cohort study sheds light that biological and environmental factors may partly underlie race/ethnicity-related differences in young-onset noncardia gastric cancer susceptibility and outcomes.

Project description:ImportanceGastric cancer is the fifth most common cancer worldwide, and investigating its incidence, characteristics, treatment, and outcomes over the past decades can help in selecting clinical strategies and future research directions.ObjectiveTo analyze the trends in incidence, staging, and treatment of gastric cancer.Design, setting, and participantsThis nationwide, population-based cohort study included patients diagnosed with noncardia gastric cancer (NCGC) between 1989 and 2021 in the Netherlands.Main outcomes and measuresDifferences in tumor characteristics, treatment, and survival were analyzed per fixed time periods (1989-1993, 1994-1998, 1999-2003, 2004-2008, 2009-2013, 2014-2018, and 2019-2021).ResultsIn total, 47 014 patients (median [IQR] age, 73 [64-80] years; 28 032 [60%] male patients) were identified with mostly adenocarcinomas of the antrum region (when location was known). Age-standardized incidence decreased from 20.3 to 6.1 per 100 000 person-years between 1989 and 2021. During the study period, unknown T and N stages were recorded less frequently, and metastatic disease was diagnosed more frequently (1989-1993: 2633 of 9493 patients [28%]; 2019-2021: 1503 of 3200 patients [47%] in 2019-2021). Over time, fewer patients with metastatic disease underwent surgery with or without other treatment modalities (68% in 1989-1993 vs 64% in 2019-2021), and palliative chemotherapy in metastatic NCGC increased from 9% to 40%. For patients with nonmetastatic disease, 5-year relative survival improved from 28% (95% CI, 26.5%-29.2%) to 36% (95% CI, 33.5%-37.6%) between 1989 and 2021. For patients with nonmetastatic disease undergoing a resection, 5-year survival increased from 40% (95% CI, 38.3%-41.8%) to 51% (95% CI, 47.9%-53.3%). For patients with metastatic disease, 1-year relative survival increased from 10% (95% CI, 8.7%-11.1%) to 19% (95% CI, 17.2%-21.6%), but 3-year relative survival remained poor at 5% (95% CI, 3.6%-7.5%).Conclusions and relevanceIn this nationwide cohort study involving 47 014 patients diagnosed with NCGC (1989-2021), the results showed a decrease in incidence, more accurate staging, a shift in treatment modalities, and improved patient survival.

Project description:ObjectiveBoth variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.MethodsWe genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.ResultsThe IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] = 17.76 [6.17-51.06]) or the -592C (OR [95% CI] = 8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction = 0.080).ConclusionsInflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.

Dataset Information

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

Publications

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

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