Survival Outcomes In Hepatocellular Carcinoma Patients Research Articles

High expression of MAGE-A9 correlates with unfavorable survival in hepatocellular carcinoma.

Melanoma-associated antigens (MAGE)-A9 has been reported to play important roles in the development of human cancers. However, the association between MAGE-A9 expression and the clinicopathological characteristics of hepatocellular carcinoma (HCC) is not well understood. The study was to detect the expression of MAGE-A9 in human HCC and investigate the association between its expression and the clinicopathological characteristics of HCC. Reverse transcription-polymerase chain reaction (RT-PCR), one-step quantitative -PCR (qPCR) and immunohistochemistry (IHC) analyses were performed to characterize the expression of MAGE-A9 in HCC cell lines and tissues. Kaplan-Meier survival and Cox regression analyses were employed to evaluate the prognosis of 100 HCC patients. The results showed that the expression of MAGE-A9 in HCC was significantly higher than that in non-cancerous cells and tissues. Moreover, the expression level of the MAGE-A9 protein in HCC was related to the pathological grade (p = 0.003), portal vein invasion (p = 0.001), distant metastasis (p = 0.022) and TNM stage (p = 0.005). Cox regression analysis further revealed that MAGE-A9 expression is an independent prognostic factor for disease-free survival (p = 0.006) and overall survival (p = 0.022). These data are the first to indicate that MAGE-A9 expression is a valuable prognostic biomarker for HCC and that high MAGE-A9 expression suggests unfavorable survival outcomes in HCC patients.

Hepatitis B viral load affects prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself. The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function. Hepatitis B virus (HBV) is an established major risk factor of HCC development, and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC. High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways. First, it is associated with more frequent recurrence of HBV-related HCC after treatment. Second, it is associated with more occurrence and severity of potentially life-threatening HBV reactivation. Last, it is associated with more worsened liver function, which limits the therapeutic options for HBV-related HCC. HBV, directly or indirectly, can induce hepatocarcinogenesis. In patients with a high HBV DNA level and subsequent active hepatitis, adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis. HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes. Thus, high HBV viral load can affect the prognosis of patients with HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression. Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC. Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression, it is expected that long-term antiviral therapy results in the sustained HBV suppression, control of inflammation, reduction in HCC progression, and eventually in improved overall survival.

Interrelationships among genetic C677T polymorphism of 5,10‐methylenetetrahydrofolate reductase, biochemical folate status, and lymphocytic p53 oxidative damage in association with tumor malignancy and survivals of patients with hepatocellular carcinoma

Metabolic genotypes of 5,10-methylenetetrahydrofolate reductase (MTHFR) and folate status on oxidative DNA lesions in hepatocellular carcinoma (HCC) has not been elucidated. The aims of the study were to investigate the folate-polymorphic interactions on genetic oxidative damage in association with advanced HCC malignancy and prognosis. The study included 232 HCC patients with folate nutrition, MTHFR C677T polymorphic, p53 genetic and tumour pathological data collected and analyzed for their survivals after a 7.8-years following up. By adjustment for oxidative risk factors of HCC, the compound CT and TT genotypes in relative to the CC wild-type were associated with 83% reduced lymphocytic p53 oxidative lesions of HCC patients with RBC folate lower than 688ng/mL (OR: 0.17, 95%CI: 0.07-0.43). Such genetic protective effects by the CT/TT genotypes were 2-fold enhanced among those with high RBC folate (OR: 0.08, 95% CI: 0.03-0.21, P for interaction < 0.001). For those with non-folate-deficient status, the compound CT and TT vs. CC genotypes were associated with 80% reduced risks of advanced HCC stages (III&IV) (OR: 0.2, 95%CI: 0.08-0.56). Such protection was negated either by adjustment of lymphocytic p53 oxidative lesions or by 3-fold increased risks among those with high RBC status (OR: 0.6, 95%CI; 0.31-1.41, P for interaction = 0.009). Multivariate Cox proportional hazards analysis showed that the CT/TT genotypes vs. CC wild-type were the independent predictable factor for better survival outcome of HCC patients (HR: 0.48, CI = 0.30-0.79). For CC homozygote, the second vs. the bottom tertile levels of RBC status were associated with 2-fold increased mortality rate of HCC patients (HR: 2.05, CI = 1.0-4.1). Our data demonstrated that reduced MTHFR activities associated with the MTHFR T allele may interact with RBC folate as the risk modifiers of lymphocytic p53 oxidative lesions of HCC patients. The CT/TT genotypes correlated with lower risks of late-stage HCC and a favorable survival of HCC patients, depending on p53 oxidative lesions or RBC folate status.

Genetic C677T polymorphisms of methylenetetrahydrofolate reductase and one‐carbon metabolites as prognostic predictors for survival outcome of patients with hepatocellular carcinoma.

The aims of this study were to investigate the association between methylene‐ tetrahydrofolate reductase(MTHFR) C677T polymorphism, two thymidylate synthase(TS) polymorphylisms (a tandem‐repeat of 5′UTR and 6‐bp ins/del polymophylism on the 3′UTR), one carbon‐status and survival rates of patients with hepatocellular carcinoma (HCC). The cohort study included 232 HCC patients. MTHFR C677T and TS polymorphisms were analyzed by real‐time PCR. Survival outcome of HCC patients was analyzed by Kaplan–Meier method and Cox proportional hazard model. The results showed that Cox elevated serum AFP (&gt;;200 vs. &lt;20, HR=3.61, CI=1.99–6.55), vitB12(&gt;;1500 vs. &lt;699, HR=2.69, CI =1.24–5.84), RBC folate (&gt;;818 vs. &lt;566, HR=2.05, CI=1.11–3.78), overweight (&gt;;24 vs. &lt;18.5, HR=4.86, CI=1.11–21.17) and increase tumor size (5~10 vs. &lt;5, HR=1.97; CI=1.18–3.27) will elevate the hazard ratio of HCC death. MTHFR 677 CT or TT genotypes were associated with reduced hazard ratio of HCC death (CT/TT vs. CC, HR=0.48; CI=0.30–0.79). CC genotype in combination with high folate status (566–818 ng/mL) or with elevated vitamin B12 levels (699–1500 ng/ mL) were associated with increased HR (HR=2.02, 95%CI=1.00–4.11) for RBC; (HR=2.04, 95% CI=1.11–3.77) for vitamin B12. Taken together, folate, B12 and MTHFR C677T polymorphism serve as the potential predictors for survival outcome of HCC patients.