Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization

Background—Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the grade-independent association between AKs and SCC has been suggested; however, the molecular bases of this potential association have not been in...

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Autores principales:	Valeria Righi, Camilla Reggiani, Elisabetta Tarentini, Adele Mucci, Alessia Paganelli, Anna Maria Cesinaro, Ema Mataca, Shaniko Kaleci, Barbara Ferrari, Marco Meleti, Cristina Magnoni
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	human skin metabolomics actinic keratosis squamous cell carcinoma metabolomic NMR profiling histology biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/01be6f7b21604a1391210e91960b6a6e
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spelling	oai:doaj.org-article:01be6f7b21604a1391210e91960b6a6e2021-11-11T15:35:02ZMetabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization10.3390/cancers132155602072-6694https://doaj.org/article/01be6f7b21604a1391210e91960b6a6e2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5560https://doaj.org/toc/2072-6694Background—Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the grade-independent association between AKs and SCC has been suggested; however, the molecular bases of this potential association have not been investigated. This study has assessed the metabolomic fingerprint of AK I, AK II, AK III and SCC using high resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in order to evaluate the hypothesis of grade-independent association between AK and SCC. Association between AKs and SCCs has also been evaluated by histopathology. Methods—Metabolomic data were obtained through HR-MAS NMR spectroscopy. The whole spectral profiles were analyzed through multivariate statistical analysis using MetaboAnalyst 5.0. Histologic examination was performed on sections stained with hematoxylin and eosin; statistical analysis was performed using STATA software version 14. Results—A group of 35 patients affected by AKs and/or SCCs and 10 healthy controls were enrolled for metabolomics analysis. Histopathological analysis was conducted on 170 specimens of SCCs and AKs (including the ones that underwent metabolomic analysis). SCCs and AK I were found to be significantly associated in terms of the content of some metabolites. Moreover, in the logistic regression model, the presence of parakeratosis in AKs appeared to be less frequently associated with SCCs, while AKs with hypertrophy had a two-fold higher risk of being associated with SCC. Conclusions—Our findings, derived from metabolomics and histopathological data, support the notion that AK I are different from healthy skin and share some different features with SCCs. This may further support the expanding notion that all AKs should be treated independently from their clinical appearance or histological grade because they may be associated with SCC.Valeria RighiCamilla ReggianiElisabetta TarentiniAdele MucciAlessia PaganelliAnna Maria CesinaroEma MatacaShaniko KaleciBarbara FerrariMarco MeletiCristina MagnoniMDPI AGarticlehuman skin metabolomicsactinic keratosissquamous cell carcinomametabolomic NMR profilinghistologybiomarkersNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5560, p 5560 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human skin metabolomics actinic keratosis squamous cell carcinoma metabolomic NMR profiling histology biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	human skin metabolomics actinic keratosis squamous cell carcinoma metabolomic NMR profiling histology biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Valeria Righi Camilla Reggiani Elisabetta Tarentini Adele Mucci Alessia Paganelli Anna Maria Cesinaro Ema Mataca Shaniko Kaleci Barbara Ferrari Marco Meleti Cristina Magnoni Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization
description	Background—Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the grade-independent association between AKs and SCC has been suggested; however, the molecular bases of this potential association have not been investigated. This study has assessed the metabolomic fingerprint of AK I, AK II, AK III and SCC using high resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in order to evaluate the hypothesis of grade-independent association between AK and SCC. Association between AKs and SCCs has also been evaluated by histopathology. Methods—Metabolomic data were obtained through HR-MAS NMR spectroscopy. The whole spectral profiles were analyzed through multivariate statistical analysis using MetaboAnalyst 5.0. Histologic examination was performed on sections stained with hematoxylin and eosin; statistical analysis was performed using STATA software version 14. Results—A group of 35 patients affected by AKs and/or SCCs and 10 healthy controls were enrolled for metabolomics analysis. Histopathological analysis was conducted on 170 specimens of SCCs and AKs (including the ones that underwent metabolomic analysis). SCCs and AK I were found to be significantly associated in terms of the content of some metabolites. Moreover, in the logistic regression model, the presence of parakeratosis in AKs appeared to be less frequently associated with SCCs, while AKs with hypertrophy had a two-fold higher risk of being associated with SCC. Conclusions—Our findings, derived from metabolomics and histopathological data, support the notion that AK I are different from healthy skin and share some different features with SCCs. This may further support the expanding notion that all AKs should be treated independently from their clinical appearance or histological grade because they may be associated with SCC.
format	article
author	Valeria Righi Camilla Reggiani Elisabetta Tarentini Adele Mucci Alessia Paganelli Anna Maria Cesinaro Ema Mataca Shaniko Kaleci Barbara Ferrari Marco Meleti Cristina Magnoni
author_facet	Valeria Righi Camilla Reggiani Elisabetta Tarentini Adele Mucci Alessia Paganelli Anna Maria Cesinaro Ema Mataca Shaniko Kaleci Barbara Ferrari Marco Meleti Cristina Magnoni
author_sort	Valeria Righi
title	Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization
title_short	Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization
title_full	Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization
title_fullStr	Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization
title_full_unstemmed	Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization
title_sort	metabolomic analysis of actinic keratosis and scc suggests a grade-independent model of squamous cancerization
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/01be6f7b21604a1391210e91960b6a6e
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Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization

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