The Clinical Impact of Death Domain-Associated Protein and Holliday Junction Recognition Protein Expression in Cancer: Unmasking the Driving Forces of Neoplasia

SIMPLE SUMMARY: DAXX and HJURP are two proteins implicated in many physiologic processes and are considered important players contributing to the pathogenesis of a multitude of tumors. The aim of the present review of the literature is to retrieve and concisely present the data from studies conducted on human tissues that explored the expression of the aforementioned molecules in various tumor types. The researchers reported the tumor-promoting or tumor-suppressing properties of the two proteins, depending on the organ of origin, and correlated their expression with clinicopathological parameters. We report that enough data currently exist designating DAXX and HJURP as important factors in many tumors’ carcinogenesis and that both represent potential biomarkers for diagnosis, estimation of patients’ prognosis, therapy monitoring as well as targets for new therapeutic interventions. ABSTRACT: Death domain-associated protein (DAXX) and Holliday junction recognition protein (HJURP) act as chaperones of H3 histone variants H3.3 and centromere protein A (CENPA), respectively, and are implicated in many physiological processes, including aging and epigenetic regulation, by controlling various genes’ transcription and subsequently protein expression. Research has highlighted both these biomolecules as participants in key procedures of tumorigenesis, including cell proliferation, chromosome instability, and oncogene expression. As cancer continues to exert a heavy impact on patients’ well-being and bears substantial socioeconomic ramifications, the discovery of novel biomarkers for timely disease detection, estimation of prognosis, and therapy monitoring remains of utmost importance. In the present review, we present data reported from studies investigating DAXX and HJURP expression, either on mRNA or protein level, in human tissue samples from various types of neoplasia. Of note, the expression of DAXX and HJURP has been associated with a multitude of clinicopathological parameters, including disease stage, tumor grade, patients’ overall and disease-free survival, as well as lymphovascular invasion. The data reveal the tumor-promoting properties of DAXX and HJURP in a number of organs as well as their potential use as diagnostic biomarkers and underline the important association between aberrations in their expression and patients’ prognosis, rendering them as possible targets of future, personalized and precise therapeutic interventions.