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Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer

BACKGROUND: To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections. METHODS: Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching...

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Autores principales: Hao, Yi, Ye, Ming, Chen, Xiaona, Zhao, Hongli, Hasim, Ayshamgul, Guo, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893763/
https://www.ncbi.nlm.nih.gov/pubmed/33602229
http://dx.doi.org/10.1186/s12935-021-01802-5
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author Hao, Yi
Ye, Ming
Chen, Xiaona
Zhao, Hongli
Hasim, Ayshamgul
Guo, Xia
author_facet Hao, Yi
Ye, Ming
Chen, Xiaona
Zhao, Hongli
Hasim, Ayshamgul
Guo, Xia
author_sort Hao, Yi
collection PubMed
description BACKGROUND: To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections. METHODS: Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers. RESULTS: While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection. CONCLUSIONS: FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01802-5.
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spelling pubmed-78937632021-02-22 Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer Hao, Yi Ye, Ming Chen, Xiaona Zhao, Hongli Hasim, Ayshamgul Guo, Xia Cancer Cell Int Primary Research BACKGROUND: To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections. METHODS: Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers. RESULTS: While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection. CONCLUSIONS: FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-01802-5. BioMed Central 2021-02-18 /pmc/articles/PMC7893763/ /pubmed/33602229 http://dx.doi.org/10.1186/s12935-021-01802-5 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Hao, Yi
Ye, Ming
Chen, Xiaona
Zhao, Hongli
Hasim, Ayshamgul
Guo, Xia
Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
title Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
title_full Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
title_fullStr Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
title_full_unstemmed Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
title_short Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer
title_sort discovery and validation of fbln1 and ant3 as potential biomarkers for early detection of cervical cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893763/
https://www.ncbi.nlm.nih.gov/pubmed/33602229
http://dx.doi.org/10.1186/s12935-021-01802-5
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