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Article ; Online: ALTERED LEVELS OF H3K9AC, H3K4ME3, AND H3K27ME3 IN PROMOTERS OF DIFFERENTIALLY EXPRESSED GENES RELATED TO INNATE IMMUNE RESPONSE IN SEPTIC PATIENTS WITH DIFFERENT CLINICAL OUTCOMES.

Falcão-Holanda, Renata Brito / Leite, Giuseppe Gianini Figueirêdo / Brunialti, Milena Karina Colo / Jasiulionis, Miriam Galvonas / Salomão, Reinaldo

Shock (Augusta, Ga.)

2023 Volume 59, Issue 6, Page(s) 882–891

Abstract: Abstract: Sepsis is one of the leading causes of morbidity and mortality worldwide. Monocytes seem to undergo functional reprogramming during sepsis, resulting in dysregulated host immune response. To clarify this dysregulation mechanism, we ... ...

Abstract	Abstract: Sepsis is one of the leading causes of morbidity and mortality worldwide. Monocytes seem to undergo functional reprogramming during sepsis, resulting in dysregulated host immune response. To clarify this dysregulation mechanism, we investigated three histone modifications found in promoters of genes involved in innate immune response, and associated these findings with gene transcription in septic patients. These results were compared with public transcriptome data of the target genes and epigenetic enzymes that modulate the histone modifications. We used peripheral blood mononuclear cell from surviving and nonsurviving septic patients, and healthy volunteers to evaluate the expression of genes involved in innate immune response and the enrichment of H3K9ac, H3K4me3, and H3K27me3 in their promoters, by RT-qPCR and ChIP, respectively. Finally, we used transcriptome data sets to validate our findings. We found alterations in the chromatin enrichment of different genes, with an increase in H3K9ac in the anti-inflammatory cytokine IL-10 and the antimicrobial gene FPR1 , as well as an increase in H3K27me3 in the IL-10 and HLA-DR promoter in nonsurvivors septic patients when compared with survivors. These alterations were partially associated with the gene expression profile. In addition, we found moderate to strong correlation between gene transcription and the enzymes that modulate these histone modifications in the transcriptome data sets. Our study, one of the pioneering by evaluating septic patients' samples, suggests that epigenetic enzymes modulate the prevalent histone marks in promoters of genes involved in the immune-inflammatory response, altering the transcription of these specific genes during sepsis. Furthermore, nonsurviving sepsis patients have a more pronounced epigenetic dysregulation compared with survivors, suggesting a more dysfunctional response.
MeSH term(s)	Humans ; Histones/metabolism ; Interleukin-10/metabolism ; Leukocytes, Mononuclear/metabolism ; Epigenesis, Genetic ; Immunity, Innate ; Sepsis/genetics
Chemical Substances	histone H3 trimethyl Lys4 ; Histones ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2023-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1185432-7
ISSN	1540-0514 ; 1073-2322
ISSN (online)	1540-0514
ISSN	1073-2322
DOI	10.1097/SHK.0000000000002131
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Article ; Online: Activation of estrogen receptor induces differential proteomic responses mainly involving migration, invasion, and tumor development pathways in human testicular embryonal carcinoma NT2/D1 cells.

Macheroni, Carla / Leite, Giuseppe Gianini Figueirêdo / Souza, Deborah Simão / Vicente, Carolina Meloni / Lacerda, José Thalles / Moraes, Maria Nathália / Juliano, Maria Aparecida / Porto, Catarina Segreti

The Journal of steroid biochemistry and molecular biology

2023 Volume 237, Page(s) 106443

Abstract: The aims of the present study were to investigate the global changes on proteome of human testicular embryonal carcinoma NT2/D1 cells treated with 17β-estradiol (E2), and the effects of this hormone on migration, invasion, and colony formation of these ... ...

Abstract	The aims of the present study were to investigate the global changes on proteome of human testicular embryonal carcinoma NT2/D1 cells treated with 17β-estradiol (E2), and the effects of this hormone on migration, invasion, and colony formation of these cells. A quantitative proteomic analysis identified the presence of 1230 proteins in both E2-treated and control cells. The analysis revealed 75 differentially abundant proteins (DAPs), out of which 43 proteins displayed a higher abundance and, 30 proteins showed a lower abundance in E2-treated NT2/D1 cancer cells. Functional analysis using IPA highlighted some activation processes such as migration, invasion, metastasis, and tumor growth. Interestingly, the treatment with E2 and ERβ-selective agonist DPN increased the migration of NT2/D1 cells. On the other hand, ERα-selective agonist PPT did not modify cell migration, indicating that ERβ is the upstream receptor involved in this process. The activation of ERβ increased the invasion and anchorage‑independent growth of NT2/D1 cells more intensely than ERα. ERα and ERβ may play overlapping roles on invasion and colony formation of these cells. Further studies are required to clarify the mechanism underlying these effects. The molecular mechanisms revealed by proteomic and functional studies might also guide the development of potential targets for a better understanding of the biology of these cells and novel treatments for non-seminoma in the future.
MeSH term(s)	Humans ; Receptors, Estrogen ; Carcinoma, Embryonal ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Estrogen Receptor beta/metabolism ; Proteomics ; Estradiol/pharmacology
Chemical Substances	Receptors, Estrogen ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2023.106443
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Article ; Online: Understanding COVID-19 progression with longitudinal peripheral blood mononuclear cell proteomics: Changes in the cellular proteome over time.

Figueirêdo Leite, Giuseppe Gianini / Colo Brunialti, Milena Karina / Peçanha-Pietrobom, Paula M / Abrão Ferreira, Paulo R / Ota-Arakaki, Jaquelina Sonoe / Cunha-Neto, Edecio / Ferreira, Bianca Lima / Ronsein, Graziella E / Tashima, Alexandre Keiji / Salomão, Reinaldo

iScience

2023 Volume 26, Issue 10, Page(s) 107824

Abstract: The clinical presentation of COVID-19 is highly variable, and understanding the underlying biological processes is crucial. This study utilized a proteomic analysis to investigate dysregulated processes in the peripheral blood mononuclear cells of ... ...

Abstract	The clinical presentation of COVID-19 is highly variable, and understanding the underlying biological processes is crucial. This study utilized a proteomic analysis to investigate dysregulated processes in the peripheral blood mononuclear cells of patients with COVID-19 compared to healthy volunteers. Samples were collected at different stages of the disease, including hospital admission, after 7 days of hospitalization, and 30 days after discharge. Metabolic pathway alterations and increased abundance of neutrophil-related proteins were observed in patients. Patients progressing to critical illness had significantly low-abundance proteins in the pentose phosphate and glycolysis pathways compared with those presenting clinical recovery. Important biological processes, such as fatty acid concentration and glucose metabolism disorder, remained altered even after 30 days of hospital discharge. Temporal proteomic changes revealed distinct pathways in critically ill and non-critically ill patients. Our study emphasizes the significance of longitudinal cellular proteomic studies in identifying disease progression-related pathways and persistent protein changes post-hospitalization.
Language	English
Publishing date	2023-09-02
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107824
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Article ; Online: HIF-1α and Hypoxia Responsive Genes are Differentially Expressed in Leukocytes From Survivors and Non-Survivors Patients During Clinical Sepsis.

Ferreira, Bianca Lima / Leite, Giuseppe Gianini Figueirêdo / Brunialti, Milena Karina Colo / Assuncao, Murillo / Azevedo, Luciano Cesar Pontes / Freitas, Flávio / Salomao, Reinaldo

Shock (Augusta, Ga.)

2021 Volume 56, Issue 1, Page(s) 80–91

Abstract: Abstract: Hypoxia inducible factor 1 alpha (HIF-1α) is linked to the metabolic and immune alterations in septic patients. Stabilization of HIF-1α by hypoxia or inflammation promotes the expression of several genes related to glycolytic metabolism, ... ...

Abstract	Abstract: Hypoxia inducible factor 1 alpha (HIF-1α) is linked to the metabolic and immune alterations in septic patients. Stabilization of HIF-1α by hypoxia or inflammation promotes the expression of several genes related to glycolytic metabolism, angiogenesis, coagulation, cell proliferation, and apoptosis. Here, we analyzed public available blood transcriptome datasets from septic patients and evaluated by PCR array the expression of HIF-1α and other hypoxia responsive genes in peripheral blood mononuclear cells from patients with sepsis secondary to community acquired infections. Samples were collected at intensive care unit admission (D0, n=29) and after 7 days follow-up (D7, n = 18); healthy volunteers (n = 10) were included as controls. Hypoxia and glycolysis were among the top scored molecular signatures in the transcriptome datasets. PCR array showed that 24 out of 78 analyzed genes were modulated in septic patients compared with healthy volunteers; most of them (23/24) were downregulated at admission. This same pattern was observed in surviving patients, while non-survivors presented more upregulated genes. EGLN1, EGLN2, and HIF1AN, inhibitors of HIF-1α activation were downregulated in patients, regardless of the outcome, while HIF-1α and other target genes, such as PDK1 and HMOX1, expression were higher in non-survivors than in survivors, mainly at D7. Non-survivor patients also presented a higher SOFA score and lower PaO2/FiO2 ratio. Our results indicate a differential modulation of hypoxia pathway in leukocytes between septic patients who survived and those who did not survive with an increased intensity at D7, which is possibly influenced by disease severity and may affect the immune response in sepsis.
MeSH term(s)	Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Gene Expression ; Humans ; Hypoxia/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Leukocytes, Mononuclear/physiology ; Male ; Middle Aged ; Sepsis/genetics
Chemical Substances	HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2021-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1185432-7
ISSN	1540-0514 ; 1073-2322
ISSN (online)	1540-0514
ISSN	1073-2322
DOI	10.1097/SHK.0000000000001694
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Article ; Online: Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function.

Ferreira, Bianca Lima / Sousa, Mônica Bragança / Leite, Giuseppe Gianini Figueirêdo / Brunialti, Milena Karina Colo / Nishiduka, Erika Sayuri / Tashima, Alexandre Keiji / van der Poll, Tom / Salomão, Reinaldo

Frontiers in immunology

2022 Volume 13, Page(s) 1051514

Abstract: Metabolic adaptations shape immune cell function. In the acute response, a metabolic switch towards glycolysis is necessary for mounting a proinflammatory response. During the clinical course of sepsis, both suppression and activation of immune responses ...

Abstract	Metabolic adaptations shape immune cell function. In the acute response, a metabolic switch towards glycolysis is necessary for mounting a proinflammatory response. During the clinical course of sepsis, both suppression and activation of immune responses take place simultaneously. Leukocytes from septic patients present inhibition of cytokine production while other functions such as phagocytosis and production of reactive oxygen species (ROS) are preserved, similarly to the
MeSH term(s)	Humans ; Endotoxins ; Proteome ; Leukocytes, Mononuclear ; Lipopolysaccharides/pharmacology ; Proteomics ; Reactive Oxygen Species ; Leukocytes ; Sepsis ; Pentose Phosphate Pathway ; Lactates ; Glucose ; Cytokines
Chemical Substances	Endotoxins ; Proteome ; Lipopolysaccharides ; Reactive Oxygen Species ; Lactates ; Glucose (IY9XDZ35W2) ; Cytokines
Language	English
Publishing date	2022-11-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1051514
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Article ; Online: The clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantation

Paula M. Peçanha-Pietrobom / Giuseppe Gianini Figueirêdo Leite / James Hunter / Paulo R. Abrão Ferreira / Marcelo N. Burattini / Nancy Bellei / Jaquelina Sonoe Ota-Arakaki / Reinaldo Salomao

PLoS ONE, Vol 16, Iss

2021 Volume 11

Abstract: Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with ... ...

Abstract	Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with moderate COVID-19 disease, including those with a history of kidney transplantation, and examined the ability of changes in routine hematologic laboratory parameters to predict and mirror the patients’ clinical course regarding the severity of their condition (classified as critical vs. non-critical) and in-hospital mortality or hospital discharge. Among the 68 patients, 20 (29%) were kidney transplanted patients (KT), and they had much higher mortality than non-kidney transplanted patients in this cohort (40% X 8.3%). Lymphocytes, neutrophils and neutrophils/lymphocytes ratio (NLR) at admission and platelets as well as the red blood cells parameters hemoglobin, hematocrit, and RDW by the time of hospital discharge or death clearly differentiated patients progressing to critical disease and those with clinical recovery. Patients with deteriorating clinical courses presented elevated and similar NLRs during the first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in the survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21). Platelets also could distinguish survivors from non-survivors among the critical patients. In conclusion, routine hematologic tests are useful to monitor the clinical course of COVID-19 patients admitted with moderate disease. Unexpectedly, changes in hematologic tests, including lymphopenia, were not predictive of complicated outcomes among KT recipients.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantation.

Paula M Peçanha-Pietrobom / Giuseppe Gianini Figueirêdo Leite / James Hunter / Paulo R Abrão Ferreira / Marcelo N Burattini / Nancy Bellei / Jaquelina Sonoe Ota-Arakaki / Reinaldo Salomao

PLoS ONE, Vol 16, Iss 11, p e

2021 Volume 0258987

Abstract	Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with moderate COVID-19 disease, including those with a history of kidney transplantation, and examined the ability of changes in routine hematologic laboratory parameters to predict and mirror the patients' clinical course regarding the severity of their condition (classified as critical vs. non-critical) and in-hospital mortality or hospital discharge. Among the 68 patients, 20 (29%) were kidney transplanted patients (KT), and they had much higher mortality than non-kidney transplanted patients in this cohort (40% X 8.3%). Lymphocytes, neutrophils and neutrophils/lymphocytes ratio (NLR) at admission and platelets as well as the red blood cells parameters hemoglobin, hematocrit, and RDW by the time of hospital discharge or death clearly differentiated patients progressing to critical disease and those with clinical recovery. Patients with deteriorating clinical courses presented elevated and similar NLRs during the first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in the survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21). Platelets also could distinguish survivors from non-survivors among the critical patients. In conclusion, routine hematologic tests are useful to monitor the clinical course of COVID-19 patients admitted with moderate disease. Unexpectedly, changes in hematologic tests, including lymphopenia, were not predictive of complicated outcomes among KT recipients.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantation.

Peçanha-Pietrobom, Paula M / Leite, Giuseppe Gianini Figueirêdo / Hunter, James / Ferreira, Paulo R Abrão / Burattini, Marcelo N / Bellei, Nancy / Ota-Arakaki, Jaquelina Sonoe / Salomao, Reinaldo

PloS one

2021 Volume 16, Issue 11, Page(s) e0258987

Abstract	Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with moderate COVID-19 disease, including those with a history of kidney transplantation, and examined the ability of changes in routine hematologic laboratory parameters to predict and mirror the patients' clinical course regarding the severity of their condition (classified as critical vs. non-critical) and in-hospital mortality or hospital discharge. Among the 68 patients, 20 (29%) were kidney transplanted patients (KT), and they had much higher mortality than non-kidney transplanted patients in this cohort (40% X 8.3%). Lymphocytes, neutrophils and neutrophils/lymphocytes ratio (NLR) at admission and platelets as well as the red blood cells parameters hemoglobin, hematocrit, and RDW by the time of hospital discharge or death clearly differentiated patients progressing to critical disease and those with clinical recovery. Patients with deteriorating clinical courses presented elevated and similar NLRs during the first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in the survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21). Platelets also could distinguish survivors from non-survivors among the critical patients. In conclusion, routine hematologic tests are useful to monitor the clinical course of COVID-19 patients admitted with moderate disease. Unexpectedly, changes in hematologic tests, including lymphopenia, were not predictive of complicated outcomes among KT recipients.
MeSH term(s)	Adult ; Aged ; Biomarkers/blood ; Blood Cells/pathology ; COVID-19/mortality ; Female ; Humans ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Prognosis ; Prospective Studies
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0258987
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Article ; Online: Combined Transcriptome and Proteome Leukocyte's Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis.

Leite, Giuseppe Gianini Figueirêdo / Ferreira, Bianca Lima / Tashima, Alexandre Keiji / Nishiduka, Erika Sayuri / Cunha-Neto, Edecio / Brunialti, Milena Karina Colo / Assuncao, Murillo / Azevedo, Luciano Cesar Pontes / Freitas, Flávio / van der Poll, Tom / Scicluna, Brendon P / Salomão, Reinaldo

Frontiers in immunology

2021 Volume 12, Page(s) 744799

Abstract: Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in "omics" technologies have provided valuable tools to unravel the mechanisms ... ...

Abstract	Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in "omics" technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co-differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down-regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up-regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host-defense system.
MeSH term(s)	Databases, Factual ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Myeloid-Derived Suppressor Cells/cytology ; Myeloid-Derived Suppressor Cells/metabolism ; Neutrophils/cytology ; Neutrophils/metabolism ; Protein Interaction Maps ; Proteomics ; Sepsis/genetics ; Sepsis/immunology ; Sepsis/metabolism
Language	English
Publishing date	2021-09-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.744799
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Article ; Online: Label-free peptide quantification coupled with in silico mapping of proteases for identification of potential serum biomarkers in gastric adenocarcinoma patients.

de Oliveira, Talita Mendes / de Lacerda, José Thalles Jocelino Gomes / Leite, Giuseppe Gianini Figueiredo / Dias, Meriellen / Mendes, Maria Anita / Kassab, Paulo / E Silva, Clisleyd Glaucielly Sales / Juliano, Maria Aparecida / Forones, Nora Manoukian

Clinical biochemistry

2020 Volume 79, Page(s) 61–69

Abstract: Objectives: We aimed to identify serum level variations in protein-derived peptides between patients diagnosed with gastric adenocarcinoma (GAC) and non-cancer persons (control) to detect the activity changes of proteases and explore the auxiliary ... ...

Abstract	Objectives: We aimed to identify serum level variations in protein-derived peptides between patients diagnosed with gastric adenocarcinoma (GAC) and non-cancer persons (control) to detect the activity changes of proteases and explore the auxiliary diagnostic value in the context of GAC physiopathology. Methods: The label-free quantitative peptidome approach was applied to identify variants in serum levels of peptides that can differentiate GAC patients from the control group. Peptide sequences were submitted against Proteasix tool predicting proteases potentially involved in their generation. The activity change of proteases was subsequently estimated based on the peptides with significantly altered relative abundance. In turn, activity change prediction of proteases was correlated with relevant protease expression data from the literature. Results: A total of 191 peptide sequences generated by the cleavage of 36 precursor proteins were identified. Using the label-free quantification approach, 33 peptides were differentially quantified (adjusted fold change ≥ 1.5 and p-value < 0.05) in which 19 were up-regulated and 14 were down-regulated in GAC samples. Of these peptides, fibrinopeptide A was significantly decreased and its phosphorylated form ADpSGEGDFLAEGGGVR was upregulated in GAC samples. Activity change prediction yielded 10 proteases including 6 Matrix Metalloproteinases (MMPs), Thrombin, Plasmin, and kallikreins 4 and 14. Among predicted proteases in our analysis, MMP-7 was presented as a more promising biomarker associated with useful assays of clinical practice for GAC diagnosis. Conclusion: Our experimental results demonstrate that the serum levels of peptides were significantly differentiated in GAC physiopathology. The hypotheses built on protease regulation could be used for further investigations to measure proteases and their activity levels that have been poorly studied for GAC diagnosis.
MeSH term(s)	Adenocarcinoma/blood ; Adenocarcinoma/diagnosis ; Adult ; Aged ; Aged, 80 and over ; Amino Acid Sequence ; Biomarkers, Tumor/blood ; Cohort Studies ; Computer Simulation ; Female ; Fibrinopeptide A/analysis ; Humans ; Male ; Matrix Metalloproteinase 7/blood ; Middle Aged ; Principal Component Analysis ; Protein Interaction Maps ; Proteome/analysis ; Serine Endopeptidases/blood ; Stomach Neoplasms/blood ; Stomach Neoplasms/diagnosis
Chemical Substances	Biomarkers, Tumor ; Proteome ; Fibrinopeptide A (25422-31-5) ; Serine Endopeptidases (EC 3.4.21.-) ; MMP7 protein, human (EC 3.4.24.23) ; Matrix Metalloproteinase 7 (EC 3.4.24.23)
Language	English
Publishing date	2020-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2020.02.010
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