Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women

Autor: Dahish Ajarim, Mehmet S. Inan, Maimoona S. Nirmal, Suad M. Bin Amer, Dilek Colak, Asma Tulbah, Namik Kaya, Taher Al-Tweigeri, Abdelmoneim Eldali, Osama Al Malik, Ben Ho Park, Albandary Al-Bakheet, Hatim A. Jeprel, Asmaa Nofal
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Oncology
Aging
Microarray
Carcinogenesis
Microarrays
Disease
medicine.disease_cause
Bioinformatics
Cohort Studies
Mice
Gene Regulatory Networks
Young adult
Oligonucleotide Array Sequence Analysis
Multidisciplinary
Systems Biology
Carcinoma
Ductal
Breast
Genomics
Middle Aged
Immunohistochemistry
Functional Genomics
Gene Expression Regulation
Neoplastic
Disease Progression
Medicine
Female
Research Article
Adult
medicine.medical_specialty
Science
Breast Neoplasms
Biology
Young Adult
Breast cancer
Species Specificity
Genome Analysis Tools
Internal medicine
Biomarkers
Tumor
medicine
Carcinoma
Animals
Humans
Regulatory Networks
Genome
Human
Computational Biology
Reproducibility of Results
Cancer
Comparative Genomics
Ductal carcinoma
medicine.disease
Signaling Networks
Carcinoma
Intraductal
Noninfiltrating
Transcriptome
Genome Expression Analysis
Genes
Neoplasm
Zdroj: PLoS ONE, Vol 8, Iss 5, p e63204 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.
Databáze: OpenAIRE
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