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The Association of Ala133Ser Polymorphism and Methylation in Ras Association Domain Family 1A Gene With Unfavorable Prognosis of Hepatocellular Carcinoma.

Feng Y, Li P, Liu Y, Sha Z, Feng L, Wang F, Mao Q, Xue W - Hepat Mon (2015)

Bottom Line: The study also found that RASSF1A methylation improves the risk of HCC.The Kaplan-Meier and multivariate analyses suggested that the poor survival of HCC patients was closely connected with hepatocirrhosis, Barcelona Clinic Liver Cancer stage, Edmondson division, RASSF1A methylation and Ala133Ser polymorphism (P < 0.001).The polymorphism and promoter methylation of RASSF1A may be a significant factor in HCC, and can be an indicator for poor prognosis in patients with HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, China.

ABSTRACT

Background: The functional and prognostic significance of Ras association domain family 1A gene (RASSF1A) on hepatocellular carcinoma (HCC) has not been well characterized.

Objectives: This study aimed to investigate the association between Ala133Ser polymorphism or promoter methylation in RASSF1A and the prognosis of HCC in Nantong City, one of the areas with the highest incidence of cancer in China.

Patients and methods: Using peripheral blood plasma, the incidence rate of RASSF1A Ala133Ser in 235 controls and subjects with 260 HCC was analyzed by the polymerase chain reaction and sequencing. We further investigated the RASSF1A methylation status in HCC and corresponding peri-tumorous normal tissues using the methylation-specific polymerase chain reaction approach.

Results: It was found that the frequency of the RASSF1A Ala133Ser T allele (Ala/Ser and Ser/Ser) genotype in HCC cases was observably higher than that of normal subjects (P < 0.001). In comparison to the Ala/Ala genotype, the T allele genotype improved the susceptibility to HCC. The study also found that RASSF1A methylation improves the risk of HCC. Furthermore, in contrast with the corresponding peri-tumorous normal tissues, we observed that the RASSF1A methylation status was markedly higher in HCC tissues (P < 0.001). The Kaplan-Meier and multivariate analyses suggested that the poor survival of HCC patients was closely connected with hepatocirrhosis, Barcelona Clinic Liver Cancer stage, Edmondson division, RASSF1A methylation and Ala133Ser polymorphism (P < 0.001).

Conclusions: The polymorphism and promoter methylation of RASSF1A may be a significant factor in HCC, and can be an indicator for poor prognosis in patients with HCC.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier Survival Analysis of Patients With Hepatocellular Carcinoma(A) The overall survival rate in patients with hepatocirrhosis was significantly lower than that in patients without hepatocirrhosis. (B) The overall survival rate in patients with G2-4 Edmondson divisions was significantly lower than that in patients with G1 Edmondson divisions. (C) The overall survival rate in patients with advanced BCLC stage was significantly lower than that in patients with early BCLC stage.(D) The overall survival rate in patients with RASSF1A methylation was significantly lower than that in patients without RASSF1A methylation. (E) The overall survival rate in patients with Ala/Ser and Ser/Ser genotype was significantly lower than that in patients with the Ala/Ala genotype.
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fig24407: Kaplan-Meier Survival Analysis of Patients With Hepatocellular Carcinoma(A) The overall survival rate in patients with hepatocirrhosis was significantly lower than that in patients without hepatocirrhosis. (B) The overall survival rate in patients with G2-4 Edmondson divisions was significantly lower than that in patients with G1 Edmondson divisions. (C) The overall survival rate in patients with advanced BCLC stage was significantly lower than that in patients with early BCLC stage.(D) The overall survival rate in patients with RASSF1A methylation was significantly lower than that in patients without RASSF1A methylation. (E) The overall survival rate in patients with Ala/Ser and Ser/Ser genotype was significantly lower than that in patients with the Ala/Ala genotype.

Mentions: Univariate and multivariate Cox regression analyses verified that hepatocirrhosis, BCLC stage, Edmondson division, RASSF1A methylation and Ala133Ser polymorphism were the strongest prediction factors of overall survival (P < 0.05) (Table 4). The Kaplan-Meier survival curves revealed that there was a significantly better prognosis for patients with HCC carrying the Ala/Ala genotype without hepatocirrhosis and RASSF1A methylation, but with early BCLC stage, well-Edmondson division (Figure 3).


The Association of Ala133Ser Polymorphism and Methylation in Ras Association Domain Family 1A Gene With Unfavorable Prognosis of Hepatocellular Carcinoma.

Feng Y, Li P, Liu Y, Sha Z, Feng L, Wang F, Mao Q, Xue W - Hepat Mon (2015)

Kaplan-Meier Survival Analysis of Patients With Hepatocellular Carcinoma(A) The overall survival rate in patients with hepatocirrhosis was significantly lower than that in patients without hepatocirrhosis. (B) The overall survival rate in patients with G2-4 Edmondson divisions was significantly lower than that in patients with G1 Edmondson divisions. (C) The overall survival rate in patients with advanced BCLC stage was significantly lower than that in patients with early BCLC stage.(D) The overall survival rate in patients with RASSF1A methylation was significantly lower than that in patients without RASSF1A methylation. (E) The overall survival rate in patients with Ala/Ser and Ser/Ser genotype was significantly lower than that in patients with the Ala/Ala genotype.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644634&req=5

fig24407: Kaplan-Meier Survival Analysis of Patients With Hepatocellular Carcinoma(A) The overall survival rate in patients with hepatocirrhosis was significantly lower than that in patients without hepatocirrhosis. (B) The overall survival rate in patients with G2-4 Edmondson divisions was significantly lower than that in patients with G1 Edmondson divisions. (C) The overall survival rate in patients with advanced BCLC stage was significantly lower than that in patients with early BCLC stage.(D) The overall survival rate in patients with RASSF1A methylation was significantly lower than that in patients without RASSF1A methylation. (E) The overall survival rate in patients with Ala/Ser and Ser/Ser genotype was significantly lower than that in patients with the Ala/Ala genotype.
Mentions: Univariate and multivariate Cox regression analyses verified that hepatocirrhosis, BCLC stage, Edmondson division, RASSF1A methylation and Ala133Ser polymorphism were the strongest prediction factors of overall survival (P < 0.05) (Table 4). The Kaplan-Meier survival curves revealed that there was a significantly better prognosis for patients with HCC carrying the Ala/Ala genotype without hepatocirrhosis and RASSF1A methylation, but with early BCLC stage, well-Edmondson division (Figure 3).

Bottom Line: The study also found that RASSF1A methylation improves the risk of HCC.The Kaplan-Meier and multivariate analyses suggested that the poor survival of HCC patients was closely connected with hepatocirrhosis, Barcelona Clinic Liver Cancer stage, Edmondson division, RASSF1A methylation and Ala133Ser polymorphism (P < 0.001).The polymorphism and promoter methylation of RASSF1A may be a significant factor in HCC, and can be an indicator for poor prognosis in patients with HCC.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, China.

ABSTRACT

Background: The functional and prognostic significance of Ras association domain family 1A gene (RASSF1A) on hepatocellular carcinoma (HCC) has not been well characterized.

Objectives: This study aimed to investigate the association between Ala133Ser polymorphism or promoter methylation in RASSF1A and the prognosis of HCC in Nantong City, one of the areas with the highest incidence of cancer in China.

Patients and methods: Using peripheral blood plasma, the incidence rate of RASSF1A Ala133Ser in 235 controls and subjects with 260 HCC was analyzed by the polymerase chain reaction and sequencing. We further investigated the RASSF1A methylation status in HCC and corresponding peri-tumorous normal tissues using the methylation-specific polymerase chain reaction approach.

Results: It was found that the frequency of the RASSF1A Ala133Ser T allele (Ala/Ser and Ser/Ser) genotype in HCC cases was observably higher than that of normal subjects (P < 0.001). In comparison to the Ala/Ala genotype, the T allele genotype improved the susceptibility to HCC. The study also found that RASSF1A methylation improves the risk of HCC. Furthermore, in contrast with the corresponding peri-tumorous normal tissues, we observed that the RASSF1A methylation status was markedly higher in HCC tissues (P < 0.001). The Kaplan-Meier and multivariate analyses suggested that the poor survival of HCC patients was closely connected with hepatocirrhosis, Barcelona Clinic Liver Cancer stage, Edmondson division, RASSF1A methylation and Ala133Ser polymorphism (P < 0.001).

Conclusions: The polymorphism and promoter methylation of RASSF1A may be a significant factor in HCC, and can be an indicator for poor prognosis in patients with HCC.

No MeSH data available.


Related in: MedlinePlus