Journal of Clinical Trials, Pathology and Case StudiesJournal of Clinical Trials, Pathology and Case StudiesJournal of Clinical Trials, Pathology and Case StudiesJournal of Clinical Trials, Pathology and Case Studies2578-224XOmmega Online PublishersNew Jersey, USA1050Research ArticleInvestigating Predictive Models Based on Circulating Cell-free INK4A DNA Methylation, Alpha-fetoprotein, Platelet Count, and Age for Diagnosis and Prognosis of Hepatocellular CarcinomaInvestigating Predictive Models Based on Circulating Cell-free INK4A DNA Methylation, Alpha-fetoprotein, Platelet Count, and Age for Diagnosis and Prognosis of Hepatocellular CarcinomaRebeccaE. Waters 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 Editor* E-mail: reewater@utmb.edu
The authors have declared that no competing interests exist.
20162109201611JCPM-16-RA-105017082016090920162016Creative Commons Attribution LicenseThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. nbsp 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 lt 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 gt 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 10