FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients

BackgroundFOXO3, a member of the FOX transcription factor family, is frequently described as being deregulated in cancer. Additionally, notable role of FOXO3 can be easily recognized in the process of ageing and survival. Even though various studies have been done to acknowledge the tumour-suppressi...

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Main Authors: Mohammad Aasif Khan, Sadaf, Irfan Ahmad, Abdulaziz A. Aloliqi, Alaa Abdulaziz Eisa, Mohammad Zeeshan Najm, Maria Habib, Saad Mustafa, Sheersh Massey, Zoya Malik, Kumari Sunita, Jogendra Singh Pawar, Naseem Akhter, N. K. Shukla, S.V.S. Deo, Syed Akhtar Husain
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1078051/full
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author Mohammad Aasif Khan
Mohammad Aasif Khan
Sadaf
Irfan Ahmad
Abdulaziz A. Aloliqi
Alaa Abdulaziz Eisa
Mohammad Zeeshan Najm
Maria Habib
Saad Mustafa
Sheersh Massey
Zoya Malik
Kumari Sunita
Jogendra Singh Pawar
Naseem Akhter
N. K. Shukla
S.V.S. Deo
Syed Akhtar Husain
author_facet Mohammad Aasif Khan
Mohammad Aasif Khan
Sadaf
Irfan Ahmad
Abdulaziz A. Aloliqi
Alaa Abdulaziz Eisa
Mohammad Zeeshan Najm
Maria Habib
Saad Mustafa
Sheersh Massey
Zoya Malik
Kumari Sunita
Jogendra Singh Pawar
Naseem Akhter
N. K. Shukla
S.V.S. Deo
Syed Akhtar Husain
author_sort Mohammad Aasif Khan
collection DOAJ
description BackgroundFOXO3, a member of the FOX transcription factor family, is frequently described as being deregulated in cancer. Additionally, notable role of FOXO3 can be easily recognized in the process of ageing and survival. Even though various studies have been done to acknowledge the tumour-suppressive or oncogenic role of FOXO3 in cancer, still there exist a lack of understanding in terms of cancer prognosis and treatment. Therefore, to provide better insight, our study aims to evaluate the role and function of FOXO3 in breast cancer in Indian female patients. We examined the FOXO3 expression levels in breast cancer samples by analyzing mRNA and protein expression along with its clinicopathological parameters.ResultsA total of 127 cases of breast cancer with equal normal cases (n=127) were assessed with methylation (MS-PCR), Immunohistochemistry (IHC), mRNA expression using Real-time PCR was analysed and 66.14% cases at mRNA level were found to be downregulated, while 81.10% of cases had little or very little protein expression. Our data state, the promoter hypermethylation of the FOXO3 gene and the downregulated protein expression are significantly correlated (p=0.0004). Additionally, we found a significant correlation between the level of FOXO3 mRNA with ER (p=0.04) and status of lymph node (p=0.01) along with this.ConclusionData suggests the prognostic significance and the tumour-suppressive role of FOXO3 in breast cancer cases studied in India. However, there is a need for the extended research targeting FOXO3 to measure its clinical potential and develop well-defined therapeutic strategies.
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spelling doaj.art-8ad225b817254e11a459925ebcc711f72023-01-16T05:40:16ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.10780511078051FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patientsMohammad Aasif Khan0Mohammad Aasif Khan1 Sadaf2Irfan Ahmad3Abdulaziz A. Aloliqi4Alaa Abdulaziz Eisa5Mohammad Zeeshan Najm6Maria Habib7Saad Mustafa8Sheersh Massey9Zoya Malik10Kumari Sunita11Jogendra Singh Pawar12Naseem Akhter13N. K. Shukla14S.V.S. Deo15Syed Akhtar Husain16Human Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaDepartment of Surgical Oncology BRA-IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaHuman Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaDepartment of Medical Hematology & Medical Oncology, School of Medicine, Mays Cancer Canter, San Antonio, TX, United StatesDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi ArabiaDepartment of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi ArabiaDepartment of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Medina, Saudi ArabiaHuman Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaHuman Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaHuman Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaHuman Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaHuman Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaSchool of Biosciences, Apeejay Stya University, Gurugram, IndiaDepartment of Medical Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, United StatesDepartment of Neurology, Henry ford Health System, Detroit, MI, United StatesDepartment of Neurology, Henry ford Health System, Detroit, MI, United StatesHuman Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, IndiaBackgroundFOXO3, a member of the FOX transcription factor family, is frequently described as being deregulated in cancer. Additionally, notable role of FOXO3 can be easily recognized in the process of ageing and survival. Even though various studies have been done to acknowledge the tumour-suppressive or oncogenic role of FOXO3 in cancer, still there exist a lack of understanding in terms of cancer prognosis and treatment. Therefore, to provide better insight, our study aims to evaluate the role and function of FOXO3 in breast cancer in Indian female patients. We examined the FOXO3 expression levels in breast cancer samples by analyzing mRNA and protein expression along with its clinicopathological parameters.ResultsA total of 127 cases of breast cancer with equal normal cases (n=127) were assessed with methylation (MS-PCR), Immunohistochemistry (IHC), mRNA expression using Real-time PCR was analysed and 66.14% cases at mRNA level were found to be downregulated, while 81.10% of cases had little or very little protein expression. Our data state, the promoter hypermethylation of the FOXO3 gene and the downregulated protein expression are significantly correlated (p=0.0004). Additionally, we found a significant correlation between the level of FOXO3 mRNA with ER (p=0.04) and status of lymph node (p=0.01) along with this.ConclusionData suggests the prognostic significance and the tumour-suppressive role of FOXO3 in breast cancer cases studied in India. However, there is a need for the extended research targeting FOXO3 to measure its clinical potential and develop well-defined therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fonc.2022.1078051/fullmethylationimmunohistochemistrytumorclinical diagnosisexpression
spellingShingle Mohammad Aasif Khan
Mohammad Aasif Khan
Sadaf
Irfan Ahmad
Abdulaziz A. Aloliqi
Alaa Abdulaziz Eisa
Mohammad Zeeshan Najm
Maria Habib
Saad Mustafa
Sheersh Massey
Zoya Malik
Kumari Sunita
Jogendra Singh Pawar
Naseem Akhter
N. K. Shukla
S.V.S. Deo
Syed Akhtar Husain
FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients
Frontiers in Oncology
methylation
immunohistochemistry
tumor
clinical diagnosis
expression
title FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients
title_full FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients
title_fullStr FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients
title_full_unstemmed FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients
title_short FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients
title_sort foxo3 gene hypermethylation and its marked downregulation in breast cancer cases a study on female patients
topic methylation
immunohistochemistry
tumor
clinical diagnosis
expression
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1078051/full
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