Background: Hemangiomas are characterized by rapid growth but slow regression. Prognosis and treatment urgently require the identification of serum markers to determine the proliferative potential of hemangiomas.
Methods: Using four pairs of tissue from the proliferative and involution stages of the same hemangiomas, the authors performed cDNA microarray experiments to study differential expression of genes between proliferative hemangiomas and involuting hemangiomas. Among these genes, the authors searched for possible serum markers. A novel analysis process was used to screen for up-regulated genes encoding secreted proteins. Next, the mRNA and protein expression in hemangiomas and serum levels in patients with hemangiomas were validated by quantitative reverse-transcriptase polymerase chain reaction, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay.
Results: Sixty-two up-regulated genes were detected in proliferative hemangiomas. Angiogenin, a key angiogenesis factor induced by hypoxia, was found to be a possible serum marker. Angiogenin mRNA and protein expression were validated by quantitative reverse-transcriptase polymerase chain reaction, immunohistochemistry, and Western blotting. An enzyme-linked immunosorbent assay confirmed that angiogenin serum levels correlate with the hemangioma stage. Moreover, receiver operating characteristic curve analysis indicates a high sensitivity and specificity of angiogenin for discriminating between proliferative hemangiomas and the control group and patients with venous malformations.
Conclusions: The authors report for the first time that angiogenin may be a useful serum marker for hemangiomas, and report a novel analysis process that might efficiently screen for potential serum markers of tumors by cDNA microarray analysis.