Affiliation

• ¹Department of Pathology, University of Texas Medical Branch, USA
• ²Internal Medicine, University of Texas Medical Branch, Galveston, Texas
• ³Molecular Genetic Technology Program, School of Health Sciences, University of Texas, Anderson Cancer Center, Houston, TX, USA
• ^#These authors contributed equally to this study

Corresponding Author

Jianli Dong, Department of Pathology, University of Texas Medical Branch, Clinical Services Wing 5.140, L38253, 301 University Boulevard, Galveston, Texas 77555-0743, USA, Tel: (409) 772-4866, E-mail: jidong@utmb.edu

Citation

Dong, J., et al. Investigating Predictive Models Based on Circulating Cell-free INK4A DNA Methylation, Alpha-fetoprotein, Platelet Count, and Age for Diagnosis and Prognosis of Hepatocellular Carcinoma. (2016) J Clin Trials Pathol Case Stud 1(1): 29- 34.

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© 2016 Dong, J. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.

Abstract

Background: As Hepatocellular Carcinoma (HCC) rates continue to rise in the U.S., management remains limited with lack of adequate markers to diagnose patients at early stage when there is curative therapy. Hyper methylation of CpG dinucleotides in the promoter region of inhibitor cyclin-dependent kinase 4A (INK4A) has been shown to be a potential biomarker associated with HCC. Additional laboratory measurements including total gamma globulin, alpha-fetoprotein (AFP), and platelet count levels have been suggested as potential markers for HCC. In this study, we examined the combined use of these markers in HCC and non-HCC patients to improve the diagnosis and prognosis of HCC.
Design: We examined INK4A promoter methylation using circulating cell-free DNA in serum specimens from patients with HCC and without HCC. Methylation for seven CpG sites was examined using pyrosequencing. The following additional sets of data were recorded: patient age, sex, AFP level, total gamma globulin level, platelet count, and presence or absence of viral hepatitis. Statistical analysis was performed using logistic regression procedure in Statistical Analysis System (SAS) 8.0.
Results: In our study, a total of 153 serum specimens were analyzed, all from different subjects (74 HCC and 79 non-HCC patients), 136 (89%) were male, and 17 (11%) were female. The average age was 54.5 years (standard deviation 8.68). Of the 74 subjects with HCC, 24 (32.44%) were stage 1, 18 (24.32%) were stage 2, 16 (21.62%) were stage 3, and 16 (21.62%) were stage 4. Older subjects were more likely to have HCC than the younger subjects group (means in HCC and non-HCC groups were 56 years and 52 years, respectively, p = 0.03). High AFP values were associated with HCC (means in HCC and non-HCC groups were 1583 and 318, respectively, p < 0.01) as were low platelet values (means in HCC and non-HCC groups were 131 and 151, respectively, p = 0.03). INK4A methylation was significantly associated with stage 3 and 4 HCC (odds ratio > 1000, p = 0.02). Among INK4A, AFP, platelets, gamma globulin, and age, only INK4A and AFP were statistically significant when comparing stages 1 and 2 with stages 3 and 4 [probability of stages 1 and 2 = 1/ (1 + exp(- (1.44 - 10.84* INK4A-0.00003*AFP)].
Conclusions: Older age, high AFP, and low platelet are associated HCC. Similarly, INK4A promoter methylation rates and AFP are associated with advanced HCC stage.