Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer

Abstract Purpose Over the past decades, there is a dramatic rise in the mortality and incidence rates of breast cancer globally, despite the progressive advancement of therapeutic options. Late detection of breast cancer is often the main culprit for the ineffective treatment, and death in patients....

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Main Authors: Archana Chaudhary, Manish Kumar, Lalit Mohan, Rizwanul Haque, Pankaj Prabhakar, Mohammad Shamsul Ola, Md. Margoob Ahmad
Format: Article
Language:English
Published: Springer 2025-08-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02966-6
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author Archana Chaudhary
Manish Kumar
Lalit Mohan
Rizwanul Haque
Pankaj Prabhakar
Mohammad Shamsul Ola
Md. Margoob Ahmad
author_facet Archana Chaudhary
Manish Kumar
Lalit Mohan
Rizwanul Haque
Pankaj Prabhakar
Mohammad Shamsul Ola
Md. Margoob Ahmad
author_sort Archana Chaudhary
collection DOAJ
description Abstract Purpose Over the past decades, there is a dramatic rise in the mortality and incidence rates of breast cancer globally, despite the progressive advancement of therapeutic options. Late detection of breast cancer is often the main culprit for the ineffective treatment, and death in patients. Finding breast cancer biomarkers is thus of significant importance. Epigenetic modifications are associated with up and down regulation of important biomarker in the TGF-β pathway, such as SMAD4, which may have a greater impact in the growth and poor prognosis in breast cancer. In the current investigation we are going to check how SMAD4 regulate in various Breast cancer patients? And how its epigenetic modifications play crucial role in disease prognosis? Methods Twenty eight samples of patients with proven breast cancer and the adjacent normal tissue from the same patients were analyzed for SMAD4 expression using real-time PCR and Western blot. Additionally, MS-PCR was employed to detect the epigenetic and genetic alterations. Result SMAD4 expression dropped from Grade 1 to Grade 3 breast cancer both at mRNA and protein level as justified by real time PCR as well as western blot. This down regulation of SMAD4 expression is due to its promoter methylation, which may be a major contributing reason to the dysregulated production of SMAD4 in instances of breast cancer. Conclusion According to these findings, SMAD4 status assessment in breast cancer, fine-needle biopsy specimens may offer further prognostic data. Worse prognosis was linked to reduced SMAD4 expression due to promoter methylation in Breast cancer.
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spelling doaj-art-d91e52b217e54cf4a093a2bb7c4d913d2025-08-20T03:46:15ZengSpringerDiscover Oncology2730-60112025-08-0116111110.1007/s12672-025-02966-6Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancerArchana Chaudhary0Manish Kumar1Lalit Mohan2Rizwanul Haque3Pankaj Prabhakar4Mohammad Shamsul Ola5Md. Margoob Ahmad6Department of Pharmacology, Indira Gandhi Institute of Medical SciencesDepartment of Surgical Oncology, Indira Gandhi Institute of Medical SciencesDepartment of Pharmacology, Indira Gandhi Institute of Medical SciencesDepartment of Biotechnology, Central University of South BiharDepartment of Pharmacology, Indira Gandhi Institute of Medical SciencesDepartment of Biochemistry, College of Science, King Saud UniversityDepartment of Pharmacology, Indira Gandhi Institute of Medical SciencesAbstract Purpose Over the past decades, there is a dramatic rise in the mortality and incidence rates of breast cancer globally, despite the progressive advancement of therapeutic options. Late detection of breast cancer is often the main culprit for the ineffective treatment, and death in patients. Finding breast cancer biomarkers is thus of significant importance. Epigenetic modifications are associated with up and down regulation of important biomarker in the TGF-β pathway, such as SMAD4, which may have a greater impact in the growth and poor prognosis in breast cancer. In the current investigation we are going to check how SMAD4 regulate in various Breast cancer patients? And how its epigenetic modifications play crucial role in disease prognosis? Methods Twenty eight samples of patients with proven breast cancer and the adjacent normal tissue from the same patients were analyzed for SMAD4 expression using real-time PCR and Western blot. Additionally, MS-PCR was employed to detect the epigenetic and genetic alterations. Result SMAD4 expression dropped from Grade 1 to Grade 3 breast cancer both at mRNA and protein level as justified by real time PCR as well as western blot. This down regulation of SMAD4 expression is due to its promoter methylation, which may be a major contributing reason to the dysregulated production of SMAD4 in instances of breast cancer. Conclusion According to these findings, SMAD4 status assessment in breast cancer, fine-needle biopsy specimens may offer further prognostic data. Worse prognosis was linked to reduced SMAD4 expression due to promoter methylation in Breast cancer.https://doi.org/10.1007/s12672-025-02966-6BC (Breast Cancer)SMAD4TGF-βCancer biomarker
spellingShingle Archana Chaudhary
Manish Kumar
Lalit Mohan
Rizwanul Haque
Pankaj Prabhakar
Mohammad Shamsul Ola
Md. Margoob Ahmad
Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer
Discover Oncology
BC (Breast Cancer)
SMAD4
TGF-β
Cancer biomarker
title Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer
title_full Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer
title_fullStr Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer
title_full_unstemmed Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer
title_short Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer
title_sort promoter methylation correlates with reduced smad4 expression in patients with breast cancer
topic BC (Breast Cancer)
SMAD4
TGF-β
Cancer biomarker
url https://doi.org/10.1007/s12672-025-02966-6
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AT rizwanulhaque promotermethylationcorrelateswithreducedsmad4expressioninpatientswithbreastcancer
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