Serum MLKL and RIPK3 as Potential Biomarkers in Egyptian Breast Cancer Patients and Their Prospect Diagnostic Implications
摘要
Breast cancer (BC) is one of the top five cancers in terms of incidence and mortality among women. Cell death plays an important role in BC progression because of major resistance to apoptosis in cancerous cells. Necroptosis is a new alternative emergent cell death mechanism which is induced when caspases are inhibited and is mediated by pseudokinase mixed lineage kinase domain-like protein (MLKL) and kinase activity of receptor-interacting serine/threonine-protein kinase 1and 3 (RIPK1, RIPK3). It was found that RIPK3 and MLKL are downregulated in cancerous cells in some types of cancer.
ObjectiveEvaluate serum levels of MLKL and RIPK3 in different stages of BC to clarify the role of them in diagnosis and prognosis of BC patients and examine their prospect as dynamic novel prognostic and diagnostic biomarkers.
MethodsThe study involved 23 Egyptian female patients diagnosed with early stage BC (stages 1 and 2), 25 Egyptian female patient diagnosed with advanced stage BC (stages 3 and 4), and 20 Egyptian healthy female as control group. MLKL, RIPK3, and cancer antigen 15.3 (CA15.3) serum levels were analyzed using ELISA technique.
ResultsThe results revealed significantly higher serum levels of CA15.3 and MLKL and lower serum level of RIPK3 in advanced BC Egyptian patients compared to control and early stage BC Egyptian female patients. ROC curve analysis showed that discriminative value between stages of BC is good for CA15.3, while excellent for MLKL and RIPK3.
ConclusionMLKL and RIPK3 could be promising novel prognostic biomarkers of BC.