Prognostic value of Midkine expression in patients with solid tumors: a systematic review and meta-analysis

Abstract

BackgroundAccumulated studies have shown the important role of Midkine (MDK) protein in various solid tumors and indicated its correlation with patients’ survival. This meta-analysis was performed to further explore the prognostic value of MDK expression in solid tumors.Materials and MethodsWe collected the literatures through searching PubMed, Embase and the Cochrane Library (last up to April 10, 2017) to assess the effect of MDK on survival in solid tumor patients. The STATA 12.0 software was used for the meta-analysis. Fixed-effects models or random-effects models were used to estimate the pooled hazard ratios (HRs) for overall survival (OS).ResultsA total of 2097 patients from 17 observational studies were summarized. High expression of MDK was notably associated with worse OS in solid tumor patients. (pooled HR = 1.96; 95% CI = 1.67–2.31). The subgroup analysis of tumor type demonstrated negative impact of elevated MDK on OS in most solid tumor patients (P < 0.05), while MDK had no relevance with OS in the patients with OSCC (pooled HR = 1.68; 95% CI = 0.84–3.36; P = 0.145) or HNSCC (pooled HR = 1.56; 95% CI = 0.96–2.51; P = 0.075).ConclusionsThe present meta-analysis clarifies that MDK is a potential prognostic biomarker in solid tumor patients. Future large-scale prospective clinical trials are needed to determine the prognostic value of MDK in solid tumor patients.

Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling

“…MDK expression is induced by cytokines and growth factors, mainly by TNF-α [55], and it acts through activating the NFkβ and MAPK/PI3K proliferative pathway [54]. In clinical studies, MDK was considered a potential prognostic biomarker in solid tumors [56]. In breast cancer patients, it was suggested as both a diagnostic and a prognostic biomarker [57,58].…”

Yes-Associated Protein 1 as a Novel Prognostic Biomarker for Gastrointestinal Cancer: A Meta-Analysis

“…Meta-regression and subgroup analyses were performed to further explore the potential source of heterogeneity. Funnel plot, Egger's test, and Begg's test were performed to evaluate the publication bias [ 9 ].…”

The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation

“…Elevated MK serum levels are found in patients with different tumor entities and have been shown to correlate with poor prognosis and recurrence after tumor removal [ 2 , 3 , 4 ]. The tumor cells may be the source of MK in this case, as malignant tissue often shows high MK expression [ 5 ]. The low plasma levels of MK in healthy subjects are rapidly elevated upon administration of heparin.…”

“…We have previously shown that angiogenesis is severely impaired in MK-deficient mice, suggesting that MK also regulates the bioavailability of leukocyte-derived VEGF-A for endothelial cell proliferation in capillary sprouting [ 37 ]. These findings might have a major impact on the treatment of highly vascularized tumors as well, as tumor cells are likely to produce MK [ 5 ] to promote or even induce the vascularization of the tumor tissue itself. Accordingly, MK may represent a powerful tumor target.…”

“…However, multiple studies during the last three decades clearly indicated a functional impact of MK on the adult organism as well. By far, most of the studies on MK addressed its role in malignant diseases and suggested a detrimental effect for the host [ 2 , 3 , 4 , 5 ]. A significant part of the literature on MK has shown its ability to promote inflammatory responses.…”