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MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia
The histological criteria for classifying endometrial hyperplasia (EH) are based on architectural crowding and nuclear atypia; however, diagnostic agreement among pathologists is poor. We investigated molecular biomarkers of endometrial cancer (EC) risk in women with simple hyperplasia or complex hy...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879120/ https://www.ncbi.nlm.nih.gov/pubmed/35207799 http://dx.doi.org/10.3390/jpm12020311 |
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author | Lin, Chiao-Yun Wu, Ren-Chin Yang, Lan-Yan Jung, Shih-Ming Ueng, Shir-Hwa Tang, Yun-Hsin Huang, Huei-Jean Tung, Hsiu-Jung Lin, Cheng-Tao Chen, Hsuan-Yu Chao, Angel Lai, Chyong-Huey |
author_facet | Lin, Chiao-Yun Wu, Ren-Chin Yang, Lan-Yan Jung, Shih-Ming Ueng, Shir-Hwa Tang, Yun-Hsin Huang, Huei-Jean Tung, Hsiu-Jung Lin, Cheng-Tao Chen, Hsuan-Yu Chao, Angel Lai, Chyong-Huey |
author_sort | Lin, Chiao-Yun |
collection | PubMed |
description | The histological criteria for classifying endometrial hyperplasia (EH) are based on architectural crowding and nuclear atypia; however, diagnostic agreement among pathologists is poor. We investigated molecular biomarkers of endometrial cancer (EC) risk in women with simple hyperplasia or complex hyperplasia without atypia (SH/CH-nonA). Forty-nine patients with EC preceded by SH/CH-nonA were identified, of which 23 were excluded (15 with complex atypical hyperplasia (CAH), six not consenting, one with a diagnosis < 6 months prior, and one lost to follow-up). The EH tissues of these patients were compared with those of patients with SH/CH-nonA that did not progress to EC (control) through microRNA (miRNA) array analysis, and the results were verified in an expanded cohort through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). MiRNA arrays analyses revealed 20 miRNAs that differed significantly (p < 0.05, fold change > 4) between the control (n = 12) and case (n = 6) patients. Multiplex RT-qPCR for the 20 miRNAs in the expanded cohort (94 control and 25 case patients) led to the validation of miR-30a-3p (p = 0.0009), miR-141 (p < 0.0001), miR-200a (p < 0.0001), and miR-200b (p < 0.0001) as relevant biomarkers, among which miR-141, miR-200a, and miR-200b regulate the expression of phosphatase and tensin homolog (PTEN). For the prediction of EC, the area under the curve for miR-30a-3p, miR-141, miR-200a, and miR-200b was 0.623, 0.754, 0.783, and 0.704, respectively. The percentage of complete PTEN loss was significantly higher in the case group than in the control group (24% vs. 0%, p < 0.001, Fisher’s exact test). A combination of complete PTEN loss and miR-200a provided optimal prediction performance (sensitivity = 0.760; specificity = 1.000; positive predictive value = 1.000; negative predictive value = 0.937; accuracy = 0.947). MiR-30a-3p, miR-141, miR-200a, miR-200b, and complete PTEN loss may be useful tissue biomarkers for predicting EC risk among patients with SH/CH-nonA. |
format | Online Article Text |
id | pubmed-8879120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88791202022-02-26 MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia Lin, Chiao-Yun Wu, Ren-Chin Yang, Lan-Yan Jung, Shih-Ming Ueng, Shir-Hwa Tang, Yun-Hsin Huang, Huei-Jean Tung, Hsiu-Jung Lin, Cheng-Tao Chen, Hsuan-Yu Chao, Angel Lai, Chyong-Huey J Pers Med Article The histological criteria for classifying endometrial hyperplasia (EH) are based on architectural crowding and nuclear atypia; however, diagnostic agreement among pathologists is poor. We investigated molecular biomarkers of endometrial cancer (EC) risk in women with simple hyperplasia or complex hyperplasia without atypia (SH/CH-nonA). Forty-nine patients with EC preceded by SH/CH-nonA were identified, of which 23 were excluded (15 with complex atypical hyperplasia (CAH), six not consenting, one with a diagnosis < 6 months prior, and one lost to follow-up). The EH tissues of these patients were compared with those of patients with SH/CH-nonA that did not progress to EC (control) through microRNA (miRNA) array analysis, and the results were verified in an expanded cohort through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). MiRNA arrays analyses revealed 20 miRNAs that differed significantly (p < 0.05, fold change > 4) between the control (n = 12) and case (n = 6) patients. Multiplex RT-qPCR for the 20 miRNAs in the expanded cohort (94 control and 25 case patients) led to the validation of miR-30a-3p (p = 0.0009), miR-141 (p < 0.0001), miR-200a (p < 0.0001), and miR-200b (p < 0.0001) as relevant biomarkers, among which miR-141, miR-200a, and miR-200b regulate the expression of phosphatase and tensin homolog (PTEN). For the prediction of EC, the area under the curve for miR-30a-3p, miR-141, miR-200a, and miR-200b was 0.623, 0.754, 0.783, and 0.704, respectively. The percentage of complete PTEN loss was significantly higher in the case group than in the control group (24% vs. 0%, p < 0.001, Fisher’s exact test). A combination of complete PTEN loss and miR-200a provided optimal prediction performance (sensitivity = 0.760; specificity = 1.000; positive predictive value = 1.000; negative predictive value = 0.937; accuracy = 0.947). MiR-30a-3p, miR-141, miR-200a, miR-200b, and complete PTEN loss may be useful tissue biomarkers for predicting EC risk among patients with SH/CH-nonA. MDPI 2022-02-18 /pmc/articles/PMC8879120/ /pubmed/35207799 http://dx.doi.org/10.3390/jpm12020311 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lin, Chiao-Yun Wu, Ren-Chin Yang, Lan-Yan Jung, Shih-Ming Ueng, Shir-Hwa Tang, Yun-Hsin Huang, Huei-Jean Tung, Hsiu-Jung Lin, Cheng-Tao Chen, Hsuan-Yu Chao, Angel Lai, Chyong-Huey MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia |
title | MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia |
title_full | MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia |
title_fullStr | MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia |
title_full_unstemmed | MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia |
title_short | MicroRNAs as Predictors of Future Uterine Malignancy in Endometrial Hyperplasia without Atypia |
title_sort | micrornas as predictors of future uterine malignancy in endometrial hyperplasia without atypia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879120/ https://www.ncbi.nlm.nih.gov/pubmed/35207799 http://dx.doi.org/10.3390/jpm12020311 |
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