Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses

Background: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial. Methods: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from 13 fresh est...

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Main Authors: Alaa Siddig, Wan Faiziah Wan Abdul Rahman, Siti Norasikin Mohd Nafi, Sarina Sulong, Maya Mazuwin Yahya, Tengku Ahmad Damitri Al-Astani Tengku Din, Rozaimi Razali, Kamarul Imran Musa
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/1/200
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author Alaa Siddig
Wan Faiziah Wan Abdul Rahman
Siti Norasikin Mohd Nafi
Sarina Sulong
Maya Mazuwin Yahya
Tengku Ahmad Damitri Al-Astani Tengku Din
Rozaimi Razali
Kamarul Imran Musa
author_facet Alaa Siddig
Wan Faiziah Wan Abdul Rahman
Siti Norasikin Mohd Nafi
Sarina Sulong
Maya Mazuwin Yahya
Tengku Ahmad Damitri Al-Astani Tengku Din
Rozaimi Razali
Kamarul Imran Musa
author_sort Alaa Siddig
collection DOAJ
description Background: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial. Methods: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from 13 fresh estrogen receptor (ER)-positive primary breast cancer tissues of untreated patients (7 = young age ≤45 years and 6 = old age ≥55 years). In silico validation for the differentially expressed genes (DEGs) by young-age patients was conducted using The Cancer Genome Atlas (TCGA) database. Next, we analyzed the protein expression encoded by two of the significantly down-regulated genes by young-age patients, Glycine N-acyltransferase-like 1 (<i>GLYATL-1</i>) and Ran-binding protein 3 like (<i>RANBP3L</i>), using immunohistochemical analysis in an independent cohort of 56 and 74 ER-positive pre-therapeutic primary breast cancer tissues, respectively. Results: 12 genes were significantly differentially expressed by young-age breast cancers (fold change >2 or <2- with FDR <i>p</i>-value < 0.05). TCGA data confirmed the differential expression of six genes. Protein expression analysis of GLYATL-1 and RANBP3L did not show heterogeneous expression between young and old-age breast cancer tissues. Loss of expression of GLYATL-1 was significantly (<i>p</i>-value 0.005) associated with positive lymph node status. Higher expression of RANBP3L was significantly associated with breast cancers with lower histopathological grades (<i>p</i>-value 0.038). Conclusions: At the transcriptomic level, breast cancer developed in young and old age patients seems homogenous. The variation in the transcriptomic profiles can be attributed to the other clinicopathological characteristics rather than the age of the patient.
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spelling doaj.art-b0183d4919cb4b2ea4f408a698f24c2a2023-11-30T21:20:56ZengMDPI AGBiomedicines2227-90592023-01-0111120010.3390/biomedicines11010200Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression AnalysesAlaa Siddig0Wan Faiziah Wan Abdul Rahman1Siti Norasikin Mohd Nafi2Sarina Sulong3Maya Mazuwin Yahya4Tengku Ahmad Damitri Al-Astani Tengku Din5Rozaimi Razali6Kamarul Imran Musa7Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, MalaysiaDepartment of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, MalaysiaDepartment of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, MalaysiaHuman Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, MalaysiaBreast Cancer Awareness & Research Unit, Hospital Universiti Sains Malaysia, Kelantan 16150, MalaysiaBreast Cancer Awareness & Research Unit, Hospital Universiti Sains Malaysia, Kelantan 16150, MalaysiaDepartment of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha P.O. Box 2703, QatarDepartment of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, MalaysiaBackground: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial. Methods: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from 13 fresh estrogen receptor (ER)-positive primary breast cancer tissues of untreated patients (7 = young age ≤45 years and 6 = old age ≥55 years). In silico validation for the differentially expressed genes (DEGs) by young-age patients was conducted using The Cancer Genome Atlas (TCGA) database. Next, we analyzed the protein expression encoded by two of the significantly down-regulated genes by young-age patients, Glycine N-acyltransferase-like 1 (<i>GLYATL-1</i>) and Ran-binding protein 3 like (<i>RANBP3L</i>), using immunohistochemical analysis in an independent cohort of 56 and 74 ER-positive pre-therapeutic primary breast cancer tissues, respectively. Results: 12 genes were significantly differentially expressed by young-age breast cancers (fold change >2 or <2- with FDR <i>p</i>-value < 0.05). TCGA data confirmed the differential expression of six genes. Protein expression analysis of GLYATL-1 and RANBP3L did not show heterogeneous expression between young and old-age breast cancer tissues. Loss of expression of GLYATL-1 was significantly (<i>p</i>-value 0.005) associated with positive lymph node status. Higher expression of RANBP3L was significantly associated with breast cancers with lower histopathological grades (<i>p</i>-value 0.038). Conclusions: At the transcriptomic level, breast cancer developed in young and old age patients seems homogenous. The variation in the transcriptomic profiles can be attributed to the other clinicopathological characteristics rather than the age of the patient.https://www.mdpi.com/2227-9059/11/1/200breast canceryoung agegene expressionestrogen-receptor-positivetranscriptomic profile<i>GLYATL-1</i>
spellingShingle Alaa Siddig
Wan Faiziah Wan Abdul Rahman
Siti Norasikin Mohd Nafi
Sarina Sulong
Maya Mazuwin Yahya
Tengku Ahmad Damitri Al-Astani Tengku Din
Rozaimi Razali
Kamarul Imran Musa
Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses
Biomedicines
breast cancer
young age
gene expression
estrogen-receptor-positive
transcriptomic profile
<i>GLYATL-1</i>
title Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses
title_full Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses
title_fullStr Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses
title_full_unstemmed Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses
title_short Comparing the Biology of Young versus Old Age Estrogen-Receptor-Positive Breast Cancer through Gene and Protein Expression Analyses
title_sort comparing the biology of young versus old age estrogen receptor positive breast cancer through gene and protein expression analyses
topic breast cancer
young age
gene expression
estrogen-receptor-positive
transcriptomic profile
<i>GLYATL-1</i>
url https://www.mdpi.com/2227-9059/11/1/200
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