Exploring Oxysterols and Protein Carbonylation in Cervicovaginal Secretions as Biomarkers for Cervical Cancer Development

Busra Kose; Serkan Erkanlı; Alper Koçak; Coskun Guzel; Theo Luider; Irundika H.K. Dias; A. Tarik Baykal

doi:10.1016/j.arres.2024.100111

Exploring Oxysterols and Protein Carbonylation in Cervicovaginal Secretions as Biomarkers for Cervical Cancer Development

Busra Kose
, Serkan Erkanlı
, Alper Koçak
, Coskun Guzel
, Theo Luider
, Irundika H.K. Dias^*
, A. Tarik Baykal^*

^*Corresponding author for this work

Aston Medical School

Research output: Contribution to journal › Article › peer-review

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Abstract

Cervical cancer, a major global health issue and the fourth most common cancer among women, is strongly linked to Human Papillomavirus (HPV) infection. Emerging evidence indicates that oxidative stress plays a critical role in the carcinogenesis of cervical tissue. This study investigates the relationship between oxidative stress markers—specifically oxysterols, lipid oxidation, and protein carbonylation—and the progression of cervical neoplasia. Oxysterols, which are elevated in various inflammatory diseases and cancers, were measured in cervicovaginal fluid samples using LC-MS/MS. The targeted oxysterols included 27-hydroxycholesterol (27-OHC), 7β-hydroxycholesterol (7β-OHC), 7-ketocholesterol (7-KC), and 7α,27-dihydroxycholesterol (7α,27-diOHC). Among these, 7α,27-dihydroxycholesterol was significantly increased in correlation with the severity of neoplastic stages. In parallel, protein carbonylation, an indicator of cellular oxidative stress, was assessed. Results revealed higher levels of protein carbonylation in neoplastic samples compared to non-neoplastic controls. These modifications were further analysed through redox proteomics to identify the specific proteins affected. The study demonstrates that elevated lipid oxidation and protein carbonylation in cervicovaginal secretions are linked to the development and progression of cervical cancer. Identifying these biomarkers may improve screening strategies, enabling the identification of individuals at increased risk for cervical neoplasia and guiding timely interventions.

Original language	English
Article number	100111
Number of pages	9
Journal	Advances in Redox Research
Volume	13
Early online date	12 Aug 2024
DOIs	https://doi.org/10.1016/j.arres.2024.100111
Publication status	Published - Dec 2024

Bibliographical note

Funding

This publication is based upon work from COST Action Pan-European Network in Lipidomics and EpiLipidomics (EpiLipidNET) , CA19105 , supported by COST (European Cooperation in Science and Technology. We acknowledge funding from EpiLipidNET short-term scientific mission (STSM) in May 2022 (grant code: 48cee319). BK also acknowledge funding support by The Scientific and Technological Research Council of Turkiye (TUBITAK) \u2013 2244 Industrial Ph.D. Program. IHKD would like to thank funding support from Aston University Research and Knowledge Exchange (RKE) programme. Authors would like to Acknowledge Mr Acibadem Labmed for the support provided to us regarding sample transportation and gynaecology team from Acibadem Maslak Hospital Obstetrics and Gynaecology Department, for the sample collection with an intense sense of responsibility. This publication is based upon work from COST Action Pan-European Network in Lipidomics and EpiLipidomics (EpiLipidNET), CA19105, supported by COST (European Cooperation in Science and Technology. We acknowledge funding from EpiLipidNET short-term scientific mission (STSM) in May 2022 (grant code: 48cee319). BK also acknowledge funding support by The Scientific and Technological Research Council of Turkiye (TUBITAK) \u2013 2244 Industrial Ph.D. Program. IHKD would like to thank funding support from Aston University Research and Knowledge Exchange (RKE) programme.

Funders	Funder number
Türkiye Bilimsel ve Teknolojik Araştırma Kurumu
Aston University
Acibadem Maslak Hospital Obstetrics and Gynaecology Department
European Cooperation in Science and Technology	CA19105, 48cee319

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cervical cancer
Cervicovaginal fluid
Hydroxycholesterol
Oxidative stress
Protein carbonylation

Access to Document

10.1016/j.arres.2024.100111Licence: CC BY-NC-ND 4.0

1-s2.0-S2667137924000183-main
Copyright © 2024 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Accepted author manuscript, 1 MBLicence: CC BY-NC-ND 4.0
B Kose et al_Exploring oxysterols and protein carbonylation in cervicovaginal secretions as biomarkers for cervical cancer development
Crown Copyright © 2024 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Final published version, 1.17 MBLicence: CC BY-NC-ND 4.0

Cite this

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title = "Exploring Oxysterols and Protein Carbonylation in Cervicovaginal Secretions as Biomarkers for Cervical Cancer Development",

abstract = "Cervical cancer, a major global health issue and the fourth most common cancer among women, is strongly linked to Human Papillomavirus (HPV) infection. Emerging evidence indicates that oxidative stress plays a critical role in the carcinogenesis of cervical tissue. This study investigates the relationship between oxidative stress markers—specifically oxysterols, lipid oxidation, and protein carbonylation—and the progression of cervical neoplasia. Oxysterols, which are elevated in various inflammatory diseases and cancers, were measured in cervicovaginal fluid samples using LC-MS/MS. The targeted oxysterols included 27-hydroxycholesterol (27-OHC), 7β-hydroxycholesterol (7β-OHC), 7-ketocholesterol (7-KC), and 7α,27-dihydroxycholesterol (7α,27-diOHC). Among these, 7α,27-dihydroxycholesterol was significantly increased in correlation with the severity of neoplastic stages. In parallel, protein carbonylation, an indicator of cellular oxidative stress, was assessed. Results revealed higher levels of protein carbonylation in neoplastic samples compared to non-neoplastic controls. These modifications were further analysed through redox proteomics to identify the specific proteins affected. The study demonstrates that elevated lipid oxidation and protein carbonylation in cervicovaginal secretions are linked to the development and progression of cervical cancer. Identifying these biomarkers may improve screening strategies, enabling the identification of individuals at increased risk for cervical neoplasia and guiding timely interventions.",

keywords = "Cervical cancer, Cervicovaginal fluid, Hydroxycholesterol, Oxidative stress, Protein carbonylation",

author = "Busra Kose and Serkan Erkanlı and Alper Ko{\c c}ak and Coskun Guzel and Theo Luider and Dias, \{Irundika H.K.\} and Baykal, \{A. Tarik\}",

note = "Crown Copyright {\textcopyright} 2024 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).",

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AU - Kose, Busra

AU - Erkanlı, Serkan

AU - Koçak, Alper

AU - Guzel, Coskun

AU - Luider, Theo

AU - Dias, Irundika H.K.

AU - Baykal, A. Tarik

PY - 2024/12

Y1 - 2024/12

N2 - Cervical cancer, a major global health issue and the fourth most common cancer among women, is strongly linked to Human Papillomavirus (HPV) infection. Emerging evidence indicates that oxidative stress plays a critical role in the carcinogenesis of cervical tissue. This study investigates the relationship between oxidative stress markers—specifically oxysterols, lipid oxidation, and protein carbonylation—and the progression of cervical neoplasia. Oxysterols, which are elevated in various inflammatory diseases and cancers, were measured in cervicovaginal fluid samples using LC-MS/MS. The targeted oxysterols included 27-hydroxycholesterol (27-OHC), 7β-hydroxycholesterol (7β-OHC), 7-ketocholesterol (7-KC), and 7α,27-dihydroxycholesterol (7α,27-diOHC). Among these, 7α,27-dihydroxycholesterol was significantly increased in correlation with the severity of neoplastic stages. In parallel, protein carbonylation, an indicator of cellular oxidative stress, was assessed. Results revealed higher levels of protein carbonylation in neoplastic samples compared to non-neoplastic controls. These modifications were further analysed through redox proteomics to identify the specific proteins affected. The study demonstrates that elevated lipid oxidation and protein carbonylation in cervicovaginal secretions are linked to the development and progression of cervical cancer. Identifying these biomarkers may improve screening strategies, enabling the identification of individuals at increased risk for cervical neoplasia and guiding timely interventions.

AB - Cervical cancer, a major global health issue and the fourth most common cancer among women, is strongly linked to Human Papillomavirus (HPV) infection. Emerging evidence indicates that oxidative stress plays a critical role in the carcinogenesis of cervical tissue. This study investigates the relationship between oxidative stress markers—specifically oxysterols, lipid oxidation, and protein carbonylation—and the progression of cervical neoplasia. Oxysterols, which are elevated in various inflammatory diseases and cancers, were measured in cervicovaginal fluid samples using LC-MS/MS. The targeted oxysterols included 27-hydroxycholesterol (27-OHC), 7β-hydroxycholesterol (7β-OHC), 7-ketocholesterol (7-KC), and 7α,27-dihydroxycholesterol (7α,27-diOHC). Among these, 7α,27-dihydroxycholesterol was significantly increased in correlation with the severity of neoplastic stages. In parallel, protein carbonylation, an indicator of cellular oxidative stress, was assessed. Results revealed higher levels of protein carbonylation in neoplastic samples compared to non-neoplastic controls. These modifications were further analysed through redox proteomics to identify the specific proteins affected. The study demonstrates that elevated lipid oxidation and protein carbonylation in cervicovaginal secretions are linked to the development and progression of cervical cancer. Identifying these biomarkers may improve screening strategies, enabling the identification of individuals at increased risk for cervical neoplasia and guiding timely interventions.

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KW - Cervicovaginal fluid

KW - Hydroxycholesterol

KW - Oxidative stress

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ER -

Exploring Oxysterols and Protein Carbonylation in Cervicovaginal Secretions as Biomarkers for Cervical Cancer Development

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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