ABSTRACT
Objective: Hepatocellular carcinoma (HCC) accounts for approximately 85% of all cases of liver cancer. In China, chronic hepatitis B virus-related HCC (HBV-related HCC) is the most common type of HCC. However, the majority of HBV-related HCC patients are asymptomatic, and the best opportunities for treating these patients are missed. The precise diagnosis of HBV-related HCC is crucial. The main purpose of this study was to evaluate the diagnostic value of murine double minute-2 (MDM2) promoter methylation in HBV-related HCC patients. Methods: The methylation status of the MDM2 promoter was detected by methylation-specific PCR. The MDM2 expression levels were validated by quantitative real-time PCR. Enzyme-linked immunosorbent assay was used to determine the levels of interleukin-6 (IL-6) and tumor-necrosis factor-α (TNF-α) in plasma. Results: The methylation frequency of the MDM2 promoter was decreased in HBV-related HCC patients. The MDM2 mRNA levels of patients with HBV-related HCC were higher than those of patients with liver cirrhosis and chronic hepatitis B. The plasma levels of IL-6 and TNF-α were significantly higher in HBV-related HCC patients than that in liver cirrhosis and chronic hepatitis B patients. The TNF-α levels were higher in the unmethylated MDM2 promoter group than in the methylated MDM2 promoter group in HBV-related HCC patients. Moreover, the combination of MDM2 promoter methylation and alpha-fetoprotein (AFP) improved the diagnosis of HBV-related HCC. Conclusions: Our study indicates, for the first time, that MDM2 promoter hypomethylation is present in HBV-related HCC patients. The combination of MDM2 promoter methylation and AFP can greatly improve diagnostic efficiency in HBV-related HCC, which might provide a new method for HBV-related HCC diagnosis.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Hepatitis B, Chronic/diagnosis , Liver Neoplasms/diagnosis , Proto-Oncogene Proteins c-mdm2/genetics , alpha-Fetoproteins/analysis , Adult , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , DNA Methylation , Diagnosis, Differential , Early Detection of Cancer/methods , Female , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/virology , Humans , Liver/pathology , Liver/virology , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Liver Cirrhosis/genetics , Liver Cirrhosis/virology , Liver Neoplasms/blood , Liver Neoplasms/genetics , Liver Neoplasms/virology , Male , Middle Aged , Promoter Regions, Genetic/geneticsABSTRACT
Aim: Natural killer cell receptor group 2D (NKG2D) plays an important role in the immune regulation of tumors. We speculate that DNA methylation are involved in the regulation of NKG2D gene. Methods: We investigated the methylation status of the NKG2D promoter in peripheral blood mononuclear cells of hepatocellular carcinoma (HCC) patients, chronic hepatitis B patients and healthy controls by methylation-specific PCR and the mRNA expression level was examined by real-time quantitative PCR. Results: The methylation frequency of NKG2D promoter in HCC patients was higher than that of chronic hepatitis B patients and healthy controls. NKG2D promoter methylation has a good predictive value for HCC diagnosis. Conclusion: NKG2D promoter methylation can be used as a noninvasive marker for detecting HCC.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , DNA Methylation , Hepatitis B virus/isolation & purification , Liver Neoplasms/diagnosis , NK Cell Lectin-Like Receptor Subfamily K/genetics , Area Under Curve , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/genetics , Case-Control Studies , Female , Hepatitis B/complications , Hepatitis B/pathology , Hepatitis B/virology , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Liver Neoplasms/etiology , Liver Neoplasms/genetics , Logistic Models , Male , Middle Aged , Promoter Regions, Genetic , RNA, Messenger/metabolism , ROC Curve , alpha-Fetoproteins/analysisABSTRACT
OBJECTIVE: Management of meningiomas with major dural venous sinus involvement is challenging. We present our case series and perspective on reconstruction of the sinuses. METHODS: Fifty-five patients underwent operations between 2005 and 2016 and the retrospective data were collected and analyzed. RESULTS: The cohort was younger with a mean of 51.3 years (range, 19-72 years) predominantly involving the superior sagittal sinus (44 patients). Sinus involvement was classified into group 1 (<50% of sinus, n = 28), group 2 (50%-99%, n = 8), and group 3 (total occlusion, n = 19). Venous collateralization was present in 100% of group 2 and 3 and in 36% of group 1 occlusions. Sinus pericranii was seen in 22 patients. Gross total resection was achieved in 87.2%, and sinus reconstruction followed in 38 patients (24 by direct suture and 14 by a patch graft). Pathology showed 36 (65%) World Health Organization grade I, 18 (33%) grade II, and 1 (2%) grade III tumors. During the mean follow-up of 60 months (range, 1-132 months), sinus was patent (74%) or narrowed but patent (24%) in 98%; 2 recurrences (3.6%) were observed (at 24 and 120 months). The mean preoperative/postoperative Karnofsky Performance Status and Kaplan-Meier cumulative overall/recurrence-free survival were 84.2%/88.1% and 90.9%/80.1%, respectively. CONCLUSIONS: These meningiomas present in a younger population, are more likely to be World Health Organization grade II or III, necessitating a more aggressive tumor resection strategy. Aggressive resection coupled with sinus reconstruction results in good long-term surgical outcome and low recurrence rates.
