The Trend of ripk1/ripk3 and mlkl Mediated Necroptosis Pathway in Patients with Different Stages of Prostate Cancer as Promising Progression Biomarkers.

Background: Programmed cell death is critical to maintain tissue homeostasis. Necroptosis, as well as apoptosis, has been considered as another form of regulated cell death which can be used as an effective way to overcome apoptosis-resistant tumor tissue growth. The aim of present study was to test whether or not ripk1, ripk3, or mlkl expression levels, as the key necroptotic modulators in different stages of prostate tumor growth.

Methods: Sixty-seven prostate tissues representing histologically confirmed cancer were selected. The cancer samples were categorized into 4 different stages based on cellular differentiation, tumor growth rate, and extra tissue expansion to regional lymph nodes, average PSA levels, and tumor volume. RNA extraction, cDNA synthesis and quantitative real time PCR were done based on standard guidelines.

Results: No statistically significant changes in ripk1 expression showed in all three stages (stage II to IV). The expression pattern of ripk3 represented a remarkable elevation in early stage, while, predominantly repressed in final cancer stage (IV). Also, there has been a significant negative correlation between ripk3 gene expression and tumor size and PSA levels.

Conclusions: We cannot exclude the importance of the key regulator proteins in development and progression of prevalent lethal disease like prostate cancer. The ripk1/ripk3 mediated necroptosis pathway is more activated in early stages of prostate cancer via induced ripk3 expression, while repressed during prostate cancer final stages. Also, the repression of ripk3 is related to elevation of both PSA levels and tumor volume which represented the tumor progression in final stages.