Abstract
BackgroundVasculogenic mimicry (VM) a microvascular system consisting of non-endothelial cells that is newly formed by aggressive tumors, has been proposed as an important therapeutic target in malignant melanoma (MM). We performed a systematic literature review to evaluate the diagnostic and prognostic accuracy of VM status for overall survival of MM patients.MethodsThe quality of the included studies was evaluated using the QUADAS-2 tool. Diagnostic capacity of VM variables, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under summary receiver operating characteristic (SROC), were pooled using Meta-DiSc software.ResultsA retrospective observational study was conducted based on twelve clinical studies including 978 clinically confirmed melanoma patients with proportion (P). VM+ melanoma cells were associated with poor prognosis in 38% of MM group (P = 0.35, 95% confidence intervals (CI): 0.27–0.42, p < 0.001). The pooled sensitivity and specificity were 0.82 (95% CI: 0.79–0.84) and 0.69 (95% CI: 0.66–0.71), respectively. Furthermore, the pooled PLR, NLR, and DOR were 2.56 (95% CI: 1.94–3.93), 0.17 (95% CI: 0.07–0.42), and 17.75 (95% CI: 5.30–59.44), respectively. Furthermore, the AUC of SROC was 0.63, indicating high reliability of VM status as a biomarker. Importantly, subgroup results suggested that VM+ status is a significantly accurate prognostic biomarker when diagnosed by the CD31−/PAS+ staining methods in Asian MM samples (p < 0.001).ConclusionsOur findings support the potential of VM status of tumors as a promising prognostic biomarker and emphasize an effective adjuvant therapeutic strategy in the prognosis of Asian MM patients.
Highlights
Vasculogenic mimicry (VM) a microvascular system consisting of non-endothelial cells that is newly formed by aggressive tumors, has been proposed as an important therapeutic target in malignant melanoma (MM)
Our results indicate that 38% of MM patients with VM+ have a poor prognosis (P = 0.35, 95% Confidence interval (CI): 0.27–0.42, p < 0.001)
In vivo and in vitro studies have shown that twist-related protein 1 (Twist1), neurogenic locus notch homolog protein 4 (Notch4), hypoxia inducible factor (HIF)-1a, EPH receptor A2 (EphA2), matrix metalloproteinase (MMP)-1, 2, − 9, − 14, and vascular endothelial (VE)-cadherin are potential therapeutic targets and prognostic indicators in VM+ tumor samples [22, 56]
Summary
Vasculogenic mimicry (VM) a microvascular system consisting of non-endothelial cells that is newly formed by aggressive tumors, has been proposed as an important therapeutic target in malignant melanoma (MM). Recent investigations identified a new non-angiogenesisdependent pathway entitled vasculogenic mimicry (VM), which refers to a vessel-like structure formed by extremely aggressive tumor cells that imitate endothelial cells [16, 17]. Aggressive VM+ tumor cells are characterized by a higher expression of the basement membrane extracellular matrix (ECM) components laminin5γ2 and metalloproteinases (MMPs)-1, − 2, − 9, and − 14 [21, 22, 26]. In highly aggressive melanoma cells downregulation of vascular endothelial cadherin and upregulation of ECM components promotes the perfusion of the VM pathway [19, 21]. The VM+ melanoma cells are associated with more aggressive and metastatic tumor biology
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