Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas

Zixi Yang,1 Feng Ling,1 Sibei Ruan,1 Jiajia Hu,2 Mingxi Tang,1 Xingwang Sun,1 Wenbo Long1 1Pathology Department of the First Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, Peopl...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yang Z, Ling F, Ruan S, Hu J, Tang M, Sun X, Long W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	human glioma biomarker correlation analysis genetic alteration survival rate Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/60104501b3c14ef59804d73caab93081
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:60104501b3c14ef59804d73caab93081
record_format	dspace
spelling	oai:doaj.org-article:60104501b3c14ef59804d73caab930812021-11-23T18:43:01ZClinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas1179-1322https://doaj.org/article/60104501b3c14ef59804d73caab930812021-11-01T00:00:00Zhttps://www.dovepress.com/clinical-and-prognostic-implications-of-1p19q-idh-braf-mgmt-promoter-a-peer-reviewed-fulltext-article-CMARhttps://doaj.org/toc/1179-1322Zixi Yang,1 Feng Ling,1 Sibei Ruan,1 Jiajia Hu,2 Mingxi Tang,1 Xingwang Sun,1 Wenbo Long1 1Pathology Department of the First Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Wenbo Long Email wenbolong@swmu.edu.cnBackground and Objective: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood.Methods: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II–IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry.Results: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis.Conclusion: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.Keywords: human glioma, biomarker, correlation analysis, genetic alteration, survival rateYang ZLing FRuan SHu JTang MSun XLong WDove Medical Pressarticlehuman gliomabiomarkercorrelation analysisgenetic alterationsurvival rateNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Management and Research, Vol Volume 13, Pp 8755-8765 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human glioma biomarker correlation analysis genetic alteration survival rate Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	human glioma biomarker correlation analysis genetic alteration survival rate Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yang Z Ling F Ruan S Hu J Tang M Sun X Long W Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas
description	Zixi Yang,1 Feng Ling,1 Sibei Ruan,1 Jiajia Hu,2 Mingxi Tang,1 Xingwang Sun,1 Wenbo Long1 1Pathology Department of the First Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Wenbo Long Email wenbolong@swmu.edu.cnBackground and Objective: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood.Methods: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II–IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry.Results: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis.Conclusion: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.Keywords: human glioma, biomarker, correlation analysis, genetic alteration, survival rate
format	article
author	Yang Z Ling F Ruan S Hu J Tang M Sun X Long W
author_facet	Yang Z Ling F Ruan S Hu J Tang M Sun X Long W
author_sort	Yang Z
title	Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas
title_short	Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas
title_full	Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas
title_fullStr	Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas
title_full_unstemmed	Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas
title_sort	clinical and prognostic implications of 1p/19q, idh, braf, mgmt promoter, and tert promoter alterations, and expression of ki-67 and p53 in human gliomas
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/60104501b3c14ef59804d73caab93081
work_keys_str_mv	AT yangz clinicalandprognosticimplicationsof1p19qidhbrafmgmtpromoterandtertpromoteralterationsandexpressionofki67andp53inhumangliomas AT lingf clinicalandprognosticimplicationsof1p19qidhbrafmgmtpromoterandtertpromoteralterationsandexpressionofki67andp53inhumangliomas AT ruans clinicalandprognosticimplicationsof1p19qidhbrafmgmtpromoterandtertpromoteralterationsandexpressionofki67andp53inhumangliomas AT huj clinicalandprognosticimplicationsof1p19qidhbrafmgmtpromoterandtertpromoteralterationsandexpressionofki67andp53inhumangliomas AT tangm clinicalandprognosticimplicationsof1p19qidhbrafmgmtpromoterandtertpromoteralterationsandexpressionofki67andp53inhumangliomas AT sunx clinicalandprognosticimplicationsof1p19qidhbrafmgmtpromoterandtertpromoteralterationsandexpressionofki67andp53inhumangliomas AT longw clinicalandprognosticimplicationsof1p19qidhbrafmgmtpromoterandtertpromoteralterationsandexpressionofki67andp53inhumangliomas
_version_	1718416156992208896

Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas

Ejemplares similares