Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nien-Tzu Liu, Cherng-Lih Perng, Yu-Ching Chou, Pi-Shao Ko, Yi-Jia Lin, Yu-Chun Lin, Cheng-Chang Chang, Yu-Chi Wang, Hung-Sheng Shang, Tai-Kuang Chao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/68de7029f0d844cabc4427f7f5840f73
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:68de7029f0d844cabc4427f7f5840f73
record_format	dspace
spelling	oai:doaj.org-article:68de7029f0d844cabc4427f7f5840f732021-11-11T07:14:45ZLoss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma1932-6203https://doaj.org/article/68de7029f0d844cabc4427f7f5840f732021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565757/?tool=EBIhttps://doaj.org/toc/1932-6203Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.Nien-Tzu LiuCherng-Lih PerngYu-Ching ChouPi-Shao KoYi-Jia LinYu-Chun LinCheng-Chang ChangYu-Chi WangHung-Sheng ShangTai-Kuang ChaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nien-Tzu Liu Cherng-Lih Perng Yu-Ching Chou Pi-Shao Ko Yi-Jia Lin Yu-Chun Lin Cheng-Chang Chang Yu-Chi Wang Hung-Sheng Shang Tai-Kuang Chao Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma
description	Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.
format	article
author	Nien-Tzu Liu Cherng-Lih Perng Yu-Ching Chou Pi-Shao Ko Yi-Jia Lin Yu-Chun Lin Cheng-Chang Chang Yu-Chi Wang Hung-Sheng Shang Tai-Kuang Chao
author_facet	Nien-Tzu Liu Cherng-Lih Perng Yu-Ching Chou Pi-Shao Ko Yi-Jia Lin Yu-Chun Lin Cheng-Chang Chang Yu-Chi Wang Hung-Sheng Shang Tai-Kuang Chao
author_sort	Nien-Tzu Liu
title	Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma
title_short	Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma
title_full	Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma
title_fullStr	Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma
title_full_unstemmed	Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma
title_sort	loss of ten-eleven translocation 1 (tet1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/68de7029f0d844cabc4427f7f5840f73
work_keys_str_mv	AT nientzuliu lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT chernglihperng lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT yuchingchou lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT pishaoko lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT yijialin lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT yuchunlin lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT chengchangchang lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT yuchiwang lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT hungshengshang lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma AT taikuangchao lossofteneleventranslocation1tet1expressionasadiagnosticandprognosticbiomarkerofendometrialcarcinoma
_version_	1718439407611019264

Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma

Ejemplares similares