Differentially expressed serum haptoglobin alpha chain isoforms with potential application for diagnosis of head and neck cancer

Background: The discovery of molecular biomarkers is crucial to the diagnosis of head and neck squamous cell cancer (HNSCC). Methods: Proteins from pre-surgery serum samples of patients with HNSCC and healthy individuals were analyzed by 2-dimensional gel electrophoresis (2-DE) using a 17 cm-long immobilized pH gradient gel strip (large gel). The differentially expressed protein spots were detected by statistical analysis. Because 2 haptoglobin (Hp) alpha chains were found to be differentially expressed, the genotypic distribution of Hp alpha chains in patients and healthy individuals was assayed by polymerase chain reaction. The protein expression levels of Hp alpha chains in individuals carrying different Hp alleles were analyzed by 2-DE with a small gel. Results: Two isoforms of haptoglobin alpha 2 chain (Hp alpha 2) in patients' sera were found from 2-DE analysis to be up-regulated, while the isoforms of haptoglobin alpha 1 chain (Hp alpha 1) were significantly down-regulated. Apolipoprotein All and 2 isoforms of apolipoprotein CII were also differentially expressed in the sera of patients with HNSCC. The Hp alpha 2 chain was significantly up-regulated in the patients carrying at least one haptoglobin 2 allele, according to the spot intensities from scanned images of small-gel 2-DE. Conclusions: The expression pattern of seven differentially expressed polypeptides and the up-regulation of Hp alpha 2 in individuals with the Hp 2 allele are potential biomarkers. (C) 2008 Elsevier B.V. All rights reserved.