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.

TPX2 in human clear cell renal carcinoma: Expression, function and prognostic significance

“…TPX2 is a cell cycle protein and serves a key role in the stability of the mitotic spindle (18). As a microtubule-associated protein, TPX2 tightly adheres to the mitotic spindle in mitotic cells (28).…”

“…TPX2 expression is closely regulated by the cell cycle, and exhibits particularly high expression in proliferating cells transitioning between the G 1 and S phase (12)(13)(14). Certain studies have demonstrated that the TPX2 gene, in addition to elevated gene copy numbers, is frequently identified in various human malignancies, including lung carcinoma (15), salivary gland cancer (16), esophageal cell carcinoma (17) and breast cancer (18). Furthermore, the upregulated expression of TPX2 has been observed in a number of different tumors, including bladder and colon cancer (19,20).…”

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

“…Colak et al 31 analyzed the expression signatures of breast tumors in Middle-Eastern YWBC using genomewide gene expression assays. They compared the transcriptome from BC tumors in three different age cohorts from young women (< 45 years), pre-elderly women (45-55 years) and elderly patients (> 55 years).…”

Does the patients age at cancer diagnosis affect microvessels density in uterine sarcoma tissues?

“…Starting from the well documented assumption that the tumor growth is dependent on the development of the vasculature, showing the correlation between the age of patients and the vessel density in tumors that were diagnosed can, in some way, correspond to the differences observed in some cancers concerning the dynamics of tumor growth depending on the age of a patient. Such kind of studies were conducted in breast or thyroid cancer [10][11][12].…”