A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum

Endometrial cancers (ECs) are mostly adenocarcinomas arising from the inner part of the uterus. The identification of serum biomarkers, either soluble or carried in the exosome, may be useful in making an early diagnosis. We used label-free quantification mass spectrometry (LFQ-MS)-based proteomics...

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Main Authors: Eduardo Sommella, Valeria Capaci, Michelangelo Aloisio, Emanuela Salviati, Pietro Campiglia, Giuseppe Molinario, Danilo Licastro, Giovanni Di Lorenzo, Federico Romano, Giuseppe Ricci, Lorenzo Monasta, Blendi Ura
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/24/6262
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author Eduardo Sommella
Valeria Capaci
Michelangelo Aloisio
Emanuela Salviati
Pietro Campiglia
Giuseppe Molinario
Danilo Licastro
Giovanni Di Lorenzo
Federico Romano
Giuseppe Ricci
Lorenzo Monasta
Blendi Ura
author_facet Eduardo Sommella
Valeria Capaci
Michelangelo Aloisio
Emanuela Salviati
Pietro Campiglia
Giuseppe Molinario
Danilo Licastro
Giovanni Di Lorenzo
Federico Romano
Giuseppe Ricci
Lorenzo Monasta
Blendi Ura
author_sort Eduardo Sommella
collection DOAJ
description Endometrial cancers (ECs) are mostly adenocarcinomas arising from the inner part of the uterus. The identification of serum biomarkers, either soluble or carried in the exosome, may be useful in making an early diagnosis. We used label-free quantification mass spectrometry (LFQ-MS)-based proteomics to investigate the proteome of exosomes in the albumin-depleted serum from 12 patients with EC, as compared to 12 healthy controls. After quantification and statistical analysis, we found significant changes in the abundance (<i>p</i> < 0.05) of 33 proteins in EC vs. control samples, with a fold change of ≥1.5 or ≤0.6. Validation using Western blotting analysis in 36 patients with EC as compared to 36 healthy individuals confirmed the upregulation of APOA1, HBB, CA1, HBD, LPA, SAA4, PF4V1, and APOE. A multivariate logistic regression model based on the abundance of these proteins was able to separate the controls from the EC patients with excellent sensitivity levels, particularly for stage 1 ECs. The results show that using LFQ-MS to explore the specific proteome of serum exosomes allows for the identification of biomarkers in EC. These observations suggest that PF4V1, CA1, HBD, and APOE represent biomarkers that are able to reach the clinical stage, after a validation phase.
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spelling doaj.art-43c65c2cabbd489db0972ec17a0088802023-11-24T13:49:01ZengMDPI AGCancers2072-66942022-12-011424626210.3390/cancers14246262A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer SerumEduardo Sommella0Valeria Capaci1Michelangelo Aloisio2Emanuela Salviati3Pietro Campiglia4Giuseppe Molinario5Danilo Licastro6Giovanni Di Lorenzo7Federico Romano8Giuseppe Ricci9Lorenzo Monasta10Blendi Ura11Department of Pharmacy, University of Salerno, 84084 Salerno, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyDepartment of Pharmacy, University of Salerno, 84084 Salerno, ItalyDepartment of Pharmacy, University of Salerno, 84084 Salerno, ItalyLife Sciences Department, University of Trieste, 34149 Trieste, ItalyAREA Science Park, Basovizza, 34149 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyInstitute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, ItalyEndometrial cancers (ECs) are mostly adenocarcinomas arising from the inner part of the uterus. The identification of serum biomarkers, either soluble or carried in the exosome, may be useful in making an early diagnosis. We used label-free quantification mass spectrometry (LFQ-MS)-based proteomics to investigate the proteome of exosomes in the albumin-depleted serum from 12 patients with EC, as compared to 12 healthy controls. After quantification and statistical analysis, we found significant changes in the abundance (<i>p</i> < 0.05) of 33 proteins in EC vs. control samples, with a fold change of ≥1.5 or ≤0.6. Validation using Western blotting analysis in 36 patients with EC as compared to 36 healthy individuals confirmed the upregulation of APOA1, HBB, CA1, HBD, LPA, SAA4, PF4V1, and APOE. A multivariate logistic regression model based on the abundance of these proteins was able to separate the controls from the EC patients with excellent sensitivity levels, particularly for stage 1 ECs. The results show that using LFQ-MS to explore the specific proteome of serum exosomes allows for the identification of biomarkers in EC. These observations suggest that PF4V1, CA1, HBD, and APOE represent biomarkers that are able to reach the clinical stage, after a validation phase.https://www.mdpi.com/2072-6694/14/24/6262exosomeendometrial cancerbiomarkerLFQ-MS
spellingShingle Eduardo Sommella
Valeria Capaci
Michelangelo Aloisio
Emanuela Salviati
Pietro Campiglia
Giuseppe Molinario
Danilo Licastro
Giovanni Di Lorenzo
Federico Romano
Giuseppe Ricci
Lorenzo Monasta
Blendi Ura
A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum
Cancers
exosome
endometrial cancer
biomarker
LFQ-MS
title A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum
title_full A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum
title_fullStr A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum
title_full_unstemmed A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum
title_short A Label-Free Proteomic Approach for the Identification of Biomarkers in the Exosome of Endometrial Cancer Serum
title_sort label free proteomic approach for the identification of biomarkers in the exosome of endometrial cancer serum
topic exosome
endometrial cancer
biomarker
LFQ-MS
url https://www.mdpi.com/2072-6694/14/24/6262
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