Expression and Prognostic Role of MEKK3 and pERK in Patients with Renal Clear Cell Carcinoma

Abstract

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is animportant serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate theMEK/ERK signaling pathway and promote an autocrine growth loop critical for tumor genesis, cell proliferation,terminal differentiation, apoptosis and survival. To explore the relationship between MEKK3 and cell apoptosis,clinicopathology and prognosis, we characterize the expression of MEKK3, pERK and FoxP3 in the renal clearcell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 casesof RCCC and 28 control cases. Expression levels of CD3+ ,CD3+CD4+,CD3+CD8+,CD4+CD25+, CD4+CD25+FoxP3+ were assessed by flow cytometry and analyzed for their association with pathological factors, correlationand prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCCas compared to control levels (p<0.01), associated with pathological grade (p<0.05)and clinical stage (p<0.05).CD4+CD25+ Foxp3+ Treg cells were also significantly increased in RCCC patients (p<0.05). Cox multivariateregression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognosticfactors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis andprognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpressionof pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression andclinical stage acting as independent prognostic factors.