The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15% of the BC population to BC-promoting genes, the underlying reasons for an increased occurrence of BCYW, at large, cannot be completely explained based on general risk factors for BC. This underscores the need for the development of next-generation of tissue- and body fluid-based prognostic and predictive biomarkers for BCYW. Here, we identified the genes associated with BCYW with a particular focus on the age, intrinsic BC subtypes, matched normal or normal breast tissues, and BC laterality. In young women with BC, we observed dysregulation of age-associated cancer-relevant gene sets in both cancer and normal breast tissues, sub-sets of which substantially affected the overall survival (OS) or relapse-free survival (RFS) of patients with BC and exhibited statically significant correlations with several gene modules associated with cellular processes such as the stroma, immune responses, mitotic progression, early response, and steroid responses. For example, high expression of COL1A2, COL5A2, COL5A1, NPY1R, and KIAA1644 mRNAs in the BC and normal breast tissues from young women correlated with a substantial reduction in the OS and RFS of BC patients with increased levels of these exemplified genes. Many of the genes upregulated in BCYW were overexpressed or underexpressed in normal breast tissues, which might provide clues regarding the potential involvement of such genes in the development of BC later in life. Many of BCYW-associated gene products were also found in the extracellular microvesicles/exosomes secreted from breast and other cancer cell-types as well as in body fluids such as urine, saliva, breast milk, and plasma, raising the possibility of using such approaches in the development of non-invasive, predictive and prognostic biomarkers. In conclusion, the findings of this study delineated the pathogenomics of BCYW, providing clues for future exploration of the potential predictive and prognostic importance of candidate BCYW molecules and research strategies as well as a rationale to undertake a prospective clinical study to examine some of testable hypotheses presented here. In addition, the results presented here provide a framework to bring out the importance of geographical disparities, to overcome the current bottlenecks in BCYW, and to make the next quantum leap for sporadic BCYW research and treatment.

To broaden the understanding of the epigenomic and chromatin regulation of cervical cancer, we examined the status and significance of a set of epigenomic and chromatin modifiers in cervical cancer using computational biology. We observed that 61 of 917 epigenomic and/or chromatin regulators are differentially upregulated in human cancer, including 25 upregulated in invasive squamous cell carcinomas and 29 in cervical intraepithelial neoplasia 3 (CIN3), of which 14 are upregulated in cervical intraepithelial neoplasia 2 (CIN2). Interestingly, 57 of such regulators are uniquely upregulated in cervical cancer, but not ovarian and endometrial cancers. The observed overexpression of 57 regulators was found to have a prognostic significance in cervical cancer. The collective overexpression of these regulators, as well as its subsets belonging to specific histone modifications and corresponding top ten positively co-overexpressed genes, correlated with reduced survival of patients with high expressions of the tested overexpressed regulators compared to cases with low expressions. Using cell-dependency datasets from human cervical cancer cells, we found that 20 out of 57 epigenomic and chromatin regulators studied here appeared to be essential genes, as the depletion of these genes was accompanied by the loss in cellular viability. In brief, the results presented here provide further insights into the role of epigenomic and chromatin regulators in the oncobiology of cervical cancer and broaden the list of new potential molecules of therapeutic importance.