DKK3's protective role in prostate cancer is partly due to the modulation of immune-related pathways.

While it is considered one of the most common cancers and the leading cause of death in men worldwide, prognostic stratification and treatment modalities are still limited for patients with prostate cancer (PCa). Recently, the introduction of genomic profiling and the use of new techniques like next-generation sequencing (NGS) in many cancers provide novel tools for the discovery of new molecular targets that might improve our understanding of the genomic aberrations in PCa and the discovery of novel prognostic and therapeutic targets. In this study, we investigated the possible mechanisms through which Dickkopf-3 (DKK3) produces its possible protective role in PCa using NGS in both the DKK3 overexpression PCa cell line (PC3) model and our patient cohort consisting of nine PCa and five benign prostatic hyperplasia. Interestingly, our results have shown that DKK3 transfection-modulated genes are involved in the regulation of cell motility, senescence-associated secretory phenotype (SASP), and cytokine signaling in the immune system, as well as in the regulation of adaptive immune response. Further analysis of our NGS using our in vitro model revealed the presence of 36 differentially expressed genes (DEGs) between DKK3 transfected cells and PC3 empty vector. In addition, both CP and ACE2 genes were differentially expressed not only between the transfected and empty groups but also between the transfected and Mock cells. The top common DEGs between the DKK3 overexpression cell line and our patient cohort are the following: IL32, IRAK1, RIOK1, HIST1H2BB, SNORA31, AKR1B1, ACE2, and CP. The upregulated genes including IL32, HIST1H2BB, and SNORA31 showed tumor suppressor functions in various cancers including PCa. On the other hand, both IRAK1 and RIOK1 were downregulated and involved in tumor initiation, tumor progression, poor outcome, and radiotherapy resistance. Together, our results highlighted the possible role of the DKK3-related genes in protecting against PCa initiation and progression.

Transthoracic echocardiography for arrhythmic mitral valve prolapse: Phenotypic characterization as first step.

Mitral valve prolapse (MVP) is the most frequent valvulopathy with a prevalence of 1.2%-2.4% in general population and it is characterized by a benign course. Although it can be associated with some complications, ventricular arrhythmias (VA) and sudden cardiac death (SCD) as ultimate expressions, are the most worrying. The estimated risk of SCD in MVP is between 0.2% and 1.9% per year including both MVP patients with left ventricular (LV) dysfunction due to severe MR and MVP patients without significant MR. The latter ones constitute a particular phenotype called "malignant MVP" characterized by bileaflet myxomatous prolapse, ECG repolarization abnormalities and complex VAs (c-VAs) with polymorphic/right bundle branch block morphology (RBBB) and LV fibrosis of the papillary muscles (PMs) and inferobasal wall secondary to mechanical stretching visualized as late gadolinium enhancement (LGE) areas by cardiac magnetic resonance (CMR). In MVP, the first diagnostic approach is transthoracic echocardiography (TTE) that defines the presence of mitral annular disjunction (MAD) which seems to be associated with "arrhythmic MVP" (AMVP). From an ECG point of view, AMVP is characterized by frequent premature ventricular contractions (PVCs) arising from one or both PMs, fascicular tissue, and outflow tract, as well as by T-wave inversion in the inferolateral leads. The aim of the present paper is to describe TTE red flags that could identify MVP patients at high risk to develop complex arrhythmias as supported by the corresponding findings of LGE-CMR and anatomy studies. TTE could be a co-partner in phenotyping high-risk arrhythmic MVP patients.