title: 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 an important serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate the MEK/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 clear cell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 cases of 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, correlation and prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCC as 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 multivariate regression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognostic factors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis and prognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpression of pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression and clinical stage acting as independent prognostic factors.
authors.affiliation: Department of Clinical Laboratory, Taizhou Central Hospital, Taizhou, China E-mail : luhongsheng00@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Lu
authors.forename: Mei-fu
authors.initials: MF
authors.lastname: Gan
authors.forename: Lan-xi
authors.initials: LX
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: He
authors.forename: Guang-min
authors.initials: GM
authors.lastname: Fan
authors.forename: Xue-quan
authors.initials: XQ
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D048748:MAP Kinase Kinase Kinase 3 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D048748:MAP Kinase Kinase Kinase 3; C482625:MAP3K3 protein, human