The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer

Senescence is a major response to cancer chemotherapy and has been linked to unfavorable therapy outcomes. Lamin B1 is a component of the nuclear lamina that plays a pivotal role in chromatin stability. Downregulation of lamin B1 represents an established biomarker for cellular senescence. However,...

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Main Authors: Tareq Saleh, Ahmad Alhesa, Mohammed El-Sadoni, Nisreen Abu Shahin, Elham Alsharaiah, Sofian Al Shboul, Heyam Awad, Sarah Bloukh, Mahmoud Al-Balas, Mohammad Alsalem, Bilal Azab, Tariq N. Aladily
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/12/3/609
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author Tareq Saleh
Ahmad Alhesa
Mohammed El-Sadoni
Nisreen Abu Shahin
Elham Alsharaiah
Sofian Al Shboul
Heyam Awad
Sarah Bloukh
Mahmoud Al-Balas
Mohammad Alsalem
Bilal Azab
Tariq N. Aladily
author_facet Tareq Saleh
Ahmad Alhesa
Mohammed El-Sadoni
Nisreen Abu Shahin
Elham Alsharaiah
Sofian Al Shboul
Heyam Awad
Sarah Bloukh
Mahmoud Al-Balas
Mohammad Alsalem
Bilal Azab
Tariq N. Aladily
author_sort Tareq Saleh
collection DOAJ
description Senescence is a major response to cancer chemotherapy and has been linked to unfavorable therapy outcomes. Lamin B1 is a component of the nuclear lamina that plays a pivotal role in chromatin stability. Downregulation of lamin B1 represents an established biomarker for cellular senescence. However, the protein expression level of lamin B1 in malignant tissue, particularly of the breast, has not been previously described. In this work, we investigated lamin B1 protein expression in normal breast epithelium, malignant breast tissue (including adjacent non-malignant tissue) and in malignant tissue exposed to neoadjuvant chemotherapy (NAC) using immunohistochemistry (IHC) in three patient groups (<i>n</i> = 15, <i>n</i> = 87, and <i>n</i> = 43, respectively). Our results indicate that lamin B1 mean positive expression was 93% in normal breast epithelium and 88% in malignant breast cells, but significantly decreased (mean: 55%, <i>p</i> < 0.001) in malignant breast tissue after exposure to NAC, suggestive of senescence induction. No significant association between lamin B1 expression and other clinicopathological characteristics or survival of breast cancer patients was recorded. To our knowledge, this is the first report that established the baseline protein expression level of lamin B1 in normal and malignant breast tissue, and its reduction following exposure to chemotherapy. In conclusion, lamin B1 downregulation can be used reliably as a component of multiple biomarker batteries to identify therapy-induced senescence (TIS) in clinical cancer.
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spelling doaj.art-2980ed65b5b44dbdaaca2bdeaba3b6dd2023-11-24T00:54:46ZengMDPI AGDiagnostics2075-44182022-02-0112360910.3390/diagnostics12030609The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast CancerTareq Saleh0Ahmad Alhesa1Mohammed El-Sadoni2Nisreen Abu Shahin3Elham Alsharaiah4Sofian Al Shboul5Heyam Awad6Sarah Bloukh7Mahmoud Al-Balas8Mohammad Alsalem9Bilal Azab10Tariq N. Aladily11Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa 13133, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, JordanDepartment of Pathology, King Hussein Medical Center, Royal Medical Service, Amman 11942, JordanDepartment of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa 13133, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, JordanDepartment of General and Specialized Surgery, Faculty of Medicine, The Hashemite University, Zarqa 13133, JordanDepartment of Anatomy and Histology, School of Medicine, The University of Jordan, Amman 11942, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, JordanSenescence is a major response to cancer chemotherapy and has been linked to unfavorable therapy outcomes. Lamin B1 is a component of the nuclear lamina that plays a pivotal role in chromatin stability. Downregulation of lamin B1 represents an established biomarker for cellular senescence. However, the protein expression level of lamin B1 in malignant tissue, particularly of the breast, has not been previously described. In this work, we investigated lamin B1 protein expression in normal breast epithelium, malignant breast tissue (including adjacent non-malignant tissue) and in malignant tissue exposed to neoadjuvant chemotherapy (NAC) using immunohistochemistry (IHC) in three patient groups (<i>n</i> = 15, <i>n</i> = 87, and <i>n</i> = 43, respectively). Our results indicate that lamin B1 mean positive expression was 93% in normal breast epithelium and 88% in malignant breast cells, but significantly decreased (mean: 55%, <i>p</i> < 0.001) in malignant breast tissue after exposure to NAC, suggestive of senescence induction. No significant association between lamin B1 expression and other clinicopathological characteristics or survival of breast cancer patients was recorded. To our knowledge, this is the first report that established the baseline protein expression level of lamin B1 in normal and malignant breast tissue, and its reduction following exposure to chemotherapy. In conclusion, lamin B1 downregulation can be used reliably as a component of multiple biomarker batteries to identify therapy-induced senescence (TIS) in clinical cancer.https://www.mdpi.com/2075-4418/12/3/609lamin B1immunohistochemistrybreast cancersenescence
spellingShingle Tareq Saleh
Ahmad Alhesa
Mohammed El-Sadoni
Nisreen Abu Shahin
Elham Alsharaiah
Sofian Al Shboul
Heyam Awad
Sarah Bloukh
Mahmoud Al-Balas
Mohammad Alsalem
Bilal Azab
Tariq N. Aladily
The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer
Diagnostics
lamin B1
immunohistochemistry
breast cancer
senescence
title The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer
title_full The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer
title_fullStr The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer
title_full_unstemmed The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer
title_short The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer
title_sort expression of the senescence associated biomarker lamin b1 in human breast cancer
topic lamin B1
immunohistochemistry
breast cancer
senescence
url https://www.mdpi.com/2075-4418/12/3/609
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