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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

Sequencing Analysis of RASSF1A in ProbandsThree representative sets of sequencing data are shown. (A) Ser/Ser genotype; (B) Ala/Ser genotype; (C) Ala/Ala genotype.
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fig24405: Sequencing Analysis of RASSF1A in ProbandsThree representative sets of sequencing data are shown. (A) Ser/Ser genotype; (B) Ala/Ser genotype; (C) Ala/Ala genotype.

Mentions: Peripheral blood plasmas taken from 235 controls and 260 HCC subjects were analyzed for the existence of Ala133Ser (Figure 1 and Table 1). The genotypic frequencies of the HCC patients (n = 260, χ2 = 3.760, P = 0.153) and controls (n = 235, χ2 = 0.188, P = 0.910) were both in the Hardy-Weinberg equilibrium. The results showed no population stratification and no sampling bias. There was a significant difference in the RASSF1A Ale133Ser T allele (Ala/Ser and Ser/Ser) genotype between the HCC patients and control subjects (23.1% vs. 10.2%, P < 0.001). With the Ala/Ala genotype as the reference, the Ala/Ser genotype increased the risk of HCC (OR = 2.385, 95% CI = 1.407 - 4.042, P = 0.001). Besides, in comparison with the Ala/Ala genotype, cases carrying the Ser/Ser genotype had an 8.440-fold increase in the risk of HCC (95% CI = 1.046 - 68.089, P = 0.017). Furthermore, Ser was found to have a significant gene dosage effect. With the Ala/Ala genotype as the reference, the OR for the T allele genotype was 2.638 (95% CI = 1.582 - 4.398, P < 0.001). Compared with the homozygote Ala/Ala and heterozygote Ala/Ser carriers, there was a significant increase in the risk of HCC in subjects with the homozygote variant of Ser/Ser of RASSF1A Ala133Ser polymorphism (OR = 7.429, 95% CI = 0.922 - 59.847, P = 0.027). The Ser frequency of RASSF1A Ala133Ser polymorphism in cases with HCC was significantly higher compared with the healthy control subjects (5.3% vs. 13.1%, P < 0.001). Furthermore, the Ala/Ala genotype in HCC peripheral blood plasma with hepatocirrhosis was more risky for patients with HCC than for healthy controls (OR = 10.189, 95% CI = 2.403 - 43.203, P < 0.001) (Table 2).


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)

Sequencing Analysis of RASSF1A in ProbandsThree representative sets of sequencing data are shown. (A) Ser/Ser genotype; (B) Ala/Ser genotype; (C) Ala/Ala genotype.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig24405: Sequencing Analysis of RASSF1A in ProbandsThree representative sets of sequencing data are shown. (A) Ser/Ser genotype; (B) Ala/Ser genotype; (C) Ala/Ala genotype.
Mentions: Peripheral blood plasmas taken from 235 controls and 260 HCC subjects were analyzed for the existence of Ala133Ser (Figure 1 and Table 1). The genotypic frequencies of the HCC patients (n = 260, χ2 = 3.760, P = 0.153) and controls (n = 235, χ2 = 0.188, P = 0.910) were both in the Hardy-Weinberg equilibrium. The results showed no population stratification and no sampling bias. There was a significant difference in the RASSF1A Ale133Ser T allele (Ala/Ser and Ser/Ser) genotype between the HCC patients and control subjects (23.1% vs. 10.2%, P < 0.001). With the Ala/Ala genotype as the reference, the Ala/Ser genotype increased the risk of HCC (OR = 2.385, 95% CI = 1.407 - 4.042, P = 0.001). Besides, in comparison with the Ala/Ala genotype, cases carrying the Ser/Ser genotype had an 8.440-fold increase in the risk of HCC (95% CI = 1.046 - 68.089, P = 0.017). Furthermore, Ser was found to have a significant gene dosage effect. With the Ala/Ala genotype as the reference, the OR for the T allele genotype was 2.638 (95% CI = 1.582 - 4.398, P < 0.001). Compared with the homozygote Ala/Ala and heterozygote Ala/Ser carriers, there was a significant increase in the risk of HCC in subjects with the homozygote variant of Ser/Ser of RASSF1A Ala133Ser polymorphism (OR = 7.429, 95% CI = 0.922 - 59.847, P = 0.027). The Ser frequency of RASSF1A Ala133Ser polymorphism in cases with HCC was significantly higher compared with the healthy control subjects (5.3% vs. 13.1%, P < 0.001). Furthermore, the Ala/Ala genotype in HCC peripheral blood plasma with hepatocirrhosis was more risky for patients with HCC than for healthy controls (OR = 10.189, 95% CI = 2.403 - 43.203, P < 0.001) (Table 2).

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