A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival

The purpose of this study was to establish a gene signature that may predict CIN3 regression and that may aid in selecting patients who may safely refrain from conization. Oncomine mRNA data including 398 immune-related genes from 21 lesions with confirmed regression and 28 with persistent CIN3 were...

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Autores principales:	Mari K. Halle, Ane Cecilie Munk, Birgit Engesæter, Saleha Akbari, Astri Frafjord, Erling A. Hoivik, David Forsse, Kristine E. Fasmer, Kathrine Woie, Ingfrid S. Haldorsen, Bjørn I. Bertelsen, Emiel A. M. Janssen, Einar Gudslaugsson, Camilla Krakstad, Irene T. Øvestad
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cervical intraepithelial neoplasia (CIN) cervical cancer conization prognostic biomarker HPV test gene expression analyses Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9a9dd981aa1545cda7b41aae1d03ee74
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spelling	oai:doaj.org-article:9a9dd981aa1545cda7b41aae1d03ee742021-11-25T17:03:29ZA Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival10.3390/cancers132257372072-6694https://doaj.org/article/9a9dd981aa1545cda7b41aae1d03ee742021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5737https://doaj.org/toc/2072-6694The purpose of this study was to establish a gene signature that may predict CIN3 regression and that may aid in selecting patients who may safely refrain from conization. Oncomine mRNA data including 398 immune-related genes from 21 lesions with confirmed regression and 28 with persistent CIN3 were compared. L1000 mRNA data from a cervical cancer cohort was available for validation (<i>n</i> = 239). Transcriptomic analyses identified <i>TDO2</i> (<i>p</i> = 0.004), <i>CCL5</i> (<i>p</i> < 0.001), <i>CCL3</i> (<i>p</i> = 0.04), <i>CD38</i> (<i>p</i> = 0.02), and <i>PRF1</i> (<i>p</i> = 0.005) as upregulated, and <i>LCK</i> downregulated (<i>p</i> = 0.01) in CIN3 regression as compared to persistent CIN3 lesions. From these, a gene signature predicting CIN3 regression with a sensitivity of 91% (AUC = 0.85) was established. Transcriptomic analyses revealed proliferation as significantly linked to persistent CIN3. Within the cancer cohort, high regression signature score associated with immune activation by Gene Set enrichment Analyses (GSEA) and immune cell infiltration by histopathological evaluation (<i>p</i> < 0.001). Low signature score was associated with poor survival (<i>p</i> = 0.007) and large tumors (<i>p</i> = 0.01). In conclusion, the proposed six-gene signature predicts CIN regression and favorable cervical cancer prognosis and points to common drivers in precursors and cervical cancer lesions.Mari K. HalleAne Cecilie MunkBirgit EngesæterSaleha AkbariAstri FrafjordErling A. HoivikDavid ForsseKristine E. FasmerKathrine WoieIngfrid S. HaldorsenBjørn I. BertelsenEmiel A. M. JanssenEinar GudslaugssonCamilla KrakstadIrene T. ØvestadMDPI AGarticlecervical intraepithelial neoplasia (CIN)cervical cancerconizationprognostic biomarkerHPV testgene expression analysesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5737, p 5737 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cervical intraepithelial neoplasia (CIN) cervical cancer conization prognostic biomarker HPV test gene expression analyses Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cervical intraepithelial neoplasia (CIN) cervical cancer conization prognostic biomarker HPV test gene expression analyses Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mari K. Halle Ane Cecilie Munk Birgit Engesæter Saleha Akbari Astri Frafjord Erling A. Hoivik David Forsse Kristine E. Fasmer Kathrine Woie Ingfrid S. Haldorsen Bjørn I. Bertelsen Emiel A. M. Janssen Einar Gudslaugsson Camilla Krakstad Irene T. Øvestad A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival
description	The purpose of this study was to establish a gene signature that may predict CIN3 regression and that may aid in selecting patients who may safely refrain from conization. Oncomine mRNA data including 398 immune-related genes from 21 lesions with confirmed regression and 28 with persistent CIN3 were compared. L1000 mRNA data from a cervical cancer cohort was available for validation (<i>n</i> = 239). Transcriptomic analyses identified <i>TDO2</i> (<i>p</i> = 0.004), <i>CCL5</i> (<i>p</i> < 0.001), <i>CCL3</i> (<i>p</i> = 0.04), <i>CD38</i> (<i>p</i> = 0.02), and <i>PRF1</i> (<i>p</i> = 0.005) as upregulated, and <i>LCK</i> downregulated (<i>p</i> = 0.01) in CIN3 regression as compared to persistent CIN3 lesions. From these, a gene signature predicting CIN3 regression with a sensitivity of 91% (AUC = 0.85) was established. Transcriptomic analyses revealed proliferation as significantly linked to persistent CIN3. Within the cancer cohort, high regression signature score associated with immune activation by Gene Set enrichment Analyses (GSEA) and immune cell infiltration by histopathological evaluation (<i>p</i> < 0.001). Low signature score was associated with poor survival (<i>p</i> = 0.007) and large tumors (<i>p</i> = 0.01). In conclusion, the proposed six-gene signature predicts CIN regression and favorable cervical cancer prognosis and points to common drivers in precursors and cervical cancer lesions.
format	article
author	Mari K. Halle Ane Cecilie Munk Birgit Engesæter Saleha Akbari Astri Frafjord Erling A. Hoivik David Forsse Kristine E. Fasmer Kathrine Woie Ingfrid S. Haldorsen Bjørn I. Bertelsen Emiel A. M. Janssen Einar Gudslaugsson Camilla Krakstad Irene T. Øvestad
author_facet	Mari K. Halle Ane Cecilie Munk Birgit Engesæter Saleha Akbari Astri Frafjord Erling A. Hoivik David Forsse Kristine E. Fasmer Kathrine Woie Ingfrid S. Haldorsen Bjørn I. Bertelsen Emiel A. M. Janssen Einar Gudslaugsson Camilla Krakstad Irene T. Øvestad
author_sort	Mari K. Halle
title	A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival
title_short	A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival
title_full	A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival
title_fullStr	A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival
title_full_unstemmed	A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival
title_sort	gene signature identifying cin3 regression and cervical cancer survival
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9a9dd981aa1545cda7b41aae1d03ee74
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A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival

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