Early diagnostic potential for hepatocellular carcinoma using the SELDI ProteinChip system†

Abstract

Early detection of HCC increases the potential for curative treatment and improves survival. To facilitate early detection of HCC, this study sought to identify novel diagnostic markers of HCC using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS) ProteinChip technology. Serum samples were obtained from 153 patients with or without HCC, all of whom had been diagnosed with HCV-associated chronic liver disease. To identify proteins associated with HCC, serum samples were analyzed using SELDI-TOF/MS. We constructed an initial decision tree for the correct diagnosis of HCC using serum samples from patients with (n ‫؍‬ 35) and without (n ‫؍‬ 44) HCC. Six protein peaks were selected to construct a decision tree using this first group. The efficacy of the decision tree was then assessed using a second group of patients with (n ‫؍‬ 29) and without (n ‫؍‬ 33) HCC. The sensitivity and specificity of this decision tree for the diagnosis of HCC were 83% and 76%, respectively. For a third group, we analyzed sera from seven patients with HCC obtained before the diagnosis of HCC by ultrasonography (US) and from five patients free of HCC for the past 3 years. Use of these diagnostic markers predicted the diagnosis of HCC in six of these seven patients before HCC was clinically apparent without any false positives. Conclusion: Serum profiling using the SELDI ProteinChip system is useful for the early detection and prediction of HCC in patients with chronic HCV infection. (HEPATOLOGY 2007;45:948-956.) A pproximately 170 million people worldwide are infected with HCV, which when persistent can progress to HCC. The incidence of HCC is rising; in the United States over the past 2 decades, age-specific incidence has shifted toward younger people. 1 IFN or combined IFN and ribavirin, which are currently the only effective treatments for chronic hepatitis C, reduce the occurrence of HCC. 2,3 Some patients, however, do not receive IFN treatment or fail to clear HCV even with IFN treatment. In addition, a subset of individuals remain unaware that they are infected with HCV; in these patients, HCC may present only in the advanced stage. The prognosis of patients presenting with symptoms related to HCC is extremely poor. In contrast, early detection of HCC before the onset of clinical symptoms can lead to curative treatment, significantly improving prognosis.Several methods developed for the diagnosis of HCC, including evaluation of serum markers, ultrasonography (US), computed tomography (CT), and magnetic resonance imaging, have been tested clinically. Alpha-fetoprotein (AFP) and des-gamma carboxy prothrombin (DCP), serum proteins that are elevated in HCC, have been the most widely used markers. Although routine screening offers the best chance for early tumor detection and improved survival, the reported sensitivities and specificities of elevated serum AFP and DCP levels vary significantly. [4][5][6][7][8][9] In addition, AFP levels are elevated in only 30% to 40% of patients with HCC, par...

The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma

“…The sera of all patients with and without HCC, which was confirmed by abdominal ultrasonography or computed tomography, were obtained prior to treatment. All of the sera samples from HCV-infected patients were analyzed in a previous study [15]. In addition, sera from 10 HCV-HCC patients who were diagnosed with HCC within 1 or 2 years and sera from five patients who had received radiofrequency ablation (RFA), percutaneous ethanol injection therapy (PEIT) and/or transarterial chemoembolization (TACE) for HCC were collected through a cohort study in Miyazaki.…”

“…Studies using the ProteinChip SELDI system, which is a powerful tool to discover new biomarkers, have shown that this method may be successfully used to diagnose HCC. Zinkin et al [13], Schwegler et al [14] and our research group [15] previously detected early HCC using the profile of several protein peaks that were identified by the ProteinChip SELDI system. Paradis et al [16] reported the highest discriminating peak (8900 Da), which was identified as the V10 fragment of vitronectin.…”

Serum α2-HS Glycoprotein Predicts Survival in Patients with Glioblastoma

“…We searched the serum proteome of astrocytoma patients and control subjects using SELDI-TOF mass spectrometry (MS), which has successfully identified serum biomarkers in other forms of cancer (5,6 ) and infection (7 ). A major advantage of SELDI-TOF MS is that it makes no a priori assumptions about the nature of biomarkers.…”

Correlation of serum levels of complement C4a desArg with pathologically estimated severity of glomerular lesions and mesangial hypercellularity scores in patients with IgA nephropathy

“…A comprehensive protein analysis using the ProteinChip SELDI system was performed as previously described (16,17) under the following conditions, in which several protein signals can be obtained in a stable manner. Native serum was applied to a hydrophobic cationexchange chip (CM10, Bio-Rad Laboratories, Hercules, CA, USA).…”