Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.

Since the first discovery in 1996, the engagement of TRIM28 in distinct aspects of cellular biology has been extensively studied resulting in identification of a complex nature of TRIM28 protein. In this review, we summarize core biological functions of TRIM28 that emerge from TRIM28 multi-domain structure and possessed enzymatic activities. Moreover, we will discuss whether the complexity of TRIM28 engagement in cancer biology makes TRIM28 a possible candidate for targeted anti-cancer therapy. Briefly, we will demonstrate the role of TRIM28 in regulation of target gene transcription, response to DNA damage, downregulation of p53 activity, stimulation of epithelial-to-mesenchymal transition, stemness sustainability, induction of autophagy and regulation of retrotransposition, to provide the answer whether TRIM28 functions as a stimulator or inhibitor of tumorigenesis. To date, number of studies demonstrate significant upregulation of TRIM28 expression in cancer tissues which correlates with worse overall patient survival, suggesting that TRIM28 supports cancer progression. Here, we present distinct aspects of TRIM28 involvement in regulation of cancer cell homeostasis which collectively imply pro-tumorigenic character of TRIM28. Thorough analyses are further needed to verify whether TRIM28 possess the potential to become a new anti-cancer target.