Haptoglobin and posttranslational glycan-modified derivatives as serum biomarkers for the diagnosis of nonsmall cell lung cancer.
BACKGROUND: The purpose was to evaluate the clinical utility of serum haptoglobin (Hp) and posttranslational glycan modifications of Hp for the diagnosis of nonsmall cell lung cancer (NSCLC). METHODS: Serum proteins from patients with a new diagnosis of NSCLC and age- and sex-matched controls without cancer were compared using 2-dimensional difference gel electrophoresis (2D-DIGE). Four of the differentially expressed gel spots were identified as the beta chain of Hp. Immunoblots confirmed sialyl and fucosyl group posttranslational modifications (PTMs) of Hp. Serum enzyme-linked immunosorbent assays (ELISAs) for total Hp, sialylated Hp (SAHp), and fucosylated Hp (FHp) were designed, and levels of each were measured in an independent sample set of 74 patients. Receiver operating characteristic (ROC) analysis assessed the clinical diagnostic utility of each marker. RESULTS: Statistically significant differences between lung cancer patients and matched controls were found by ELISA for Hp (P < .002), SAHp (P < .001), and FHp (P < .04). ROC analysis determined an area under the curve (AUC) of 0.754 for Hp, 0.740 for SAHp, and 0.794 for FHp. In addition, serum concentrations correlated with stage; Hp (r = 0.388; P = .018), SAHp (r = 0.300; P = .072), and FHp (r = 0.363; P = .027). CONCLUSIONS: Hp and 2 of its glycoforms, SAHp and FHp, are potentially useful in the clinical diagnosis of NSCLC. The markers increase with stage, suggesting they may also be useful in stratifying patients at presentation and in following patients after treatment.
Hoagland, LFM; Campa, MJ; Gottlin, EB; Herndon, JE; Patz, EF
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