Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma

Abstract

High preoperative serum midkine concentration is associated with poor survival in patients with esophageal cancer, even after radical surgery, and thus may have prognostic value. Midkine (MK), a heparin-binding growth factor, is expressed in numerous cancer tissues, and serum MK (S-MK) concentrations are increased in patients with various neoplasms. The aim of this study is to evaluate the clinical significance of S-MK in patients with esophageal squamous cell cancer (SCC). S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 93 patients with primary esophageal SCC before surgery. The serum concentrations of carcinoembryonic antigen (CEA), SCC antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated. All patients with esophageal SCC underwent radical esophagectomy. Tumor MK expression was assessed by immunohistochemistry in 14 fresh tumor specimens. To determine whether S-MK is of value as a prognostic factor, the authors conducted a survival analysis using Cox's proportional hazards model. S-MK values in patients with esophageal SCC were significantly higher than those in healthy controls (417 ± ± ± ±342 pg/ml vs. 154 ± ± ± ±76 pg/ml, P < < < <0.001). Using 300 pg/ml as the cut-off value (representing the mean + + + +2 standard deviations of the S-MK of healthy controls), 61% of patients with esophageal SCC were classified as positive. MK expression by the tumor was significantly associated with high level of S-MK. High S-MK ( ≥ ≥ ≥ ≥300 pg/ml) was associated with tumor size, immunoreactivity and poor survival. Multivariate analysis indicated that S-MK was an independent prognostic factor. S-MK may be a useful tumor marker for esophageal SCC. Increased preoperative S-MK in patients with esophageal SCC is associated with poor survival. (Cancer Sci 2003; 94: 628-632)

Clinical significance of midkine expression in pancreatic head carcinoma

“…In gastrointestinal stromal tumours, MK overexpression is an independent prognostic factor associated with poor prognosis (Kaifi et al, 2007). In oesophageal carcinoma, high level of serum MK is associated with tumour size, positivity rate, MK immunoreactivity, and poor survival and defined as an independent prognostic factor (Shimada et al, 2003).…”

“…In 87% of human adult carcinomas, serum MK is elevated; the level decreases after tumour removal . In oesophageal carcinoma, urinary MK is elevated , and high level of serum MK is associated with tumour progression (Obata et al, 2005), tumour size, rate of positivity for MK, MK immunoreactivity, and poor survival (Shimada et al, 2003).…”

Serum matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in esophageal cancer patients

“…Although some of tumor markers have been tested for their usefulness in diagnosis of EC patients, estimating of www.fhc.viamedica.pl prognosis, monitoring of therapy and early detection of tumor recurrence, there are no suitable tumor markers of this malignancy. SCC and CEA are the tumor markers commonly used in the diagnostics of esophageal cancer, but their diagnostic sensitivity and specificity are still unsatisfactory [23,24]. The most common technique of investigation the MMPs and TIMPs protein expression is evaluation of immunohistochemical staining, a semiquantitive and subjective method.…”

Midkine induces epithelial-mesenchymal transition through Notch2/Jak2-Stat3 signaling in human keratinocytes

“…[10][11][12][13][14] Overexpression of the full-length MK and MKC (C-terminal truncated isoform) promoted tumorigenesis in vitro and in vivo. 15,16 Since MK can promote various cellular processes (e.g., cell proliferation, survival, migration, angiogenesis, drug resistance and antiviral action) associated with cancer development, [17][18][19][20][21][22][23][24][25] identification of function-specific receptors should become an important task.…”