title: Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.
abstract: 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.
authors.affiliation: Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. dcolakkaya@kfshrc.edu.sa
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.forename: Asmaa
authors.initials: A
authors.lastname: Nofal
authors.forename: Albandary
authors.initials: A
authors.lastname: Albakheet
authors.forename: Maimoona
authors.initials: M
authors.lastname: Nirmal
authors.forename: Hatim
authors.initials: H
authors.lastname: Jeprel
authors.forename: Abdelmoneim
authors.initials: A
authors.lastname: Eldali
authors.forename: Taher
authors.initials: T
authors.lastname: Al-Tweigeri
authors.forename: Asma
authors.initials: A
authors.lastname: Tulbah
authors.forename: Dahish
authors.initials: D
authors.lastname: Ajarim
authors.forename: Osama Al
authors.initials: OA
authors.lastname: Malik
authors.forename: Mehmet S
authors.initials: MS
authors.lastname: Inan
authors.forename: Namik
authors.initials: N
authors.lastname: Kaya
authors.forename: Ben H
authors.initials: BH
authors.lastname: Park
authors.forename: Suad M
authors.initials: SM
authors.lastname: Bin Amer
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D019295:Computational Biology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D013045:Species Specificity; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor