ABSTRACT
PURPOSE: The MammaPrint™ gene signature, currently used in clinical practice, provides prognostic information regarding the recurrence and potential metastasis in breast cancer patients. However, the prognostic information of the 70 genes included can only be estimated at the RNA expression level. In this study, we investigated whether copy number information of MammaPrint™ genes at the DNA level can be used as a prognostic tool for breast cancer, as copy number variations (CNVs) are major contributors to cancer progression. METHODS: We performed CNV profiling of MammaPrint™ genes in 59 breast cancer cell lines and 650 breast cancer patients, using publicly available data in The Cancer Genome Atlas (TCGA) database. Statistical analyses including Fisher exact test, chi-square test, and Kaplan-Meier survival analyses were performed. RESULTS: All MammaPrint™ genes showed recurrent CNVs, particularly in TCGA cohort. CNVs of 32 and 36 genes showed significant associations with progesterone receptor and estrogen rector, respectively. No genes showed a significant association with human epidermal growth factor receptor 2 status and lymph node status. In addition, only six genes were associated with tumor stages. RFC4, HRASLS, NMU, GPR126, SCUBE2, C20orf46, and EBF4 were associated with reduced survival and RASSF7 and ESM1 were associated with reduced disease-free survival. CONCLUSION: Based on these findings, a concordance of CNV-based genomic rearrangement with expression profiling of these genes and their putative roles in disease tumorigenesis was established. The results suggested that the CNV profiles of the MammaPrint™ genes can be used to predict the prognosis of breast cancer patients. In addition, this approach may lead to the development of new cancer biomarkers at the DNA level.
Subject(s)
Humans , Biomarkers , Biomarkers, Tumor , Breast Neoplasms , Breast , Carcinogenesis , Cell Line , Cohort Studies , Disease-Free Survival , DNA , DNA Copy Number Variations , Estrogens , Genome , Lymph Nodes , Neoplasm Metastasis , Prognosis , ErbB Receptors , Receptors, Progesterone , Recurrence , RNAABSTRACT
Nigella sativa [N. sativa], remedial usage against different diseases associated with skeleton, cardiovascular, digestive and urinary systems has a long-standing history. At present, efforts are underway to study its effects against various cancers at both the cellular and molecular levels. In this review, the role of active constituents like thymoquinone [TQ] on different types of cancer has been explored. TQ putative involvement in metastasis has been assessed by elucidating its effects on cell proliferation, adhesion, invasion and angiogenesis. Up regulation of caspase 3, Smac and down regulation of p-AKT, p65, XIAP, Bcl-2, COX-2 is also influenced by N. sativa. These findings prove a significant positive correlation between TQ concentrations and induction of apoptosis, decrease in motility and a reduction in invasion and angiogenesis in cancerous cells. However, there are still quite a few unaddressed domains, which need to be understood. One of these may include target specificity of N. sativa against cancerous tissues, mode of administration, dosage and downstream regulators in mediating these effects. In reference to earlier findings and low cost availability, N. sativa may, also, be suggested as either a suitable sole remedy for cancer or as a complementary to ongoing conventional therapy based extensive and rigorous in vivo optimization and validation