Midkine as a prognostic biomarker in oral squamous cell carcinoma

Abstract

The aim of this study was to evaluate serum midkine (S-MK) concentrations as a prognostic tumour marker in oral squamous cell carcinoma (OSCC). We measured S-MK concentrations in patients with OSCC and healthy volunteers. In addition, we performed real-time quantitative reverse transcription -PCR analysis and immunohistochemistry with fresh tumour samples. To determine whether S-MK concentrations have prognostic value, we performed survival analyses with clinical information by using the log-rank test. Serum midkine concentrations were significantly higher in patients with OSCC than in healthy controls (Po0.001). Serum midkine concentrations were also significantly increased in early-stage OSCC compared with those of healthy individuals (Po0.001). In addition, immunohistochemistry allowed identification of overexpressed MK protein in OSCC tissues. MK mRNA showed higher expression in OSCC samples compared with normal mucosal samples. Patients in high S-MK groups showed a significantly lower 5-year survival rate compared with patients in low S-MK groups (Po0.05). The increased S-MK concentrations in early-stage OSCC were strongly associated with poor survival. Serum midkine concentrations may thus be a useful marker not only for cancer screening but also for predicting prognosis of OSCC patients.

Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma

“…In addition, MK expression has been correlated with poor prognosis in patients with neuroblastomas (18), astrocytomas (19), pancreatic cancers (17) and gastrointestinal stromal tumors (20). In a previous study, MK expression was increased in blood samples from OSCC patients and was associated with prognosis (as assessed by 5-year survival) but not with other conventional prognostic factors such as clinical stage, tumor size and cervical lymphnode metastasis (21). That report suggested that the mechanism of the association of MK with prognosis was different from that for tumor proliferation and metastasis.…”

Role of ING Family Genes in Head and Neck Cancer and Their Possible Applications in Cancer Diagnosis and Treatment

“…In a recent work, we demonstrated downregulation of TESTIN and its association with cancer history and a tendency toward poor survival in head and neck squamous cell carcinoma [96]. The increased serum midkine concentrations were strongly associated with poor survival in early-stage oral squamous cell carcinoma, suggesting it as a useful marker not only for cancer screening but also for predicting prognosis of OSCC patients [97].…”

Midkine Signaling in Glioblastoma: A Novel Developmental Drug Target?

“…The most intriguing feature of MDK is its massive expression in advanced tumors with high frequency (Qin Li et al, 2011;Kemik et al,2010). Previous reports showed that the blood MDK level is frequently elevated with advance of human carcinomas, decreased after surgical removal of the tumors (Kemik et al,2010;Ota et al, 2008;Lucas et al,2010). Glycosaminoglycan-recognizing activity of human MDK through its C-domain as heparan sulfate trisulfated unit and chondroitin sulfate E unit is important in its mechanism of action.…”