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Genetic variants in de novo lipogenic pathway genes predict the prognosis of surgically-treated hepatocellular carcinoma.

Jiang H, Dai J, Huang X, Chen Y, Qu P, Li J, Yi C, Yang Y, Zhang K, Huang Q - Sci Rep (2015)

Bottom Line: Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients.Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes.Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

ABSTRACT
Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. However, effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. A total of 492 primary HCC patients treated with surgery were included in this study. Nine SNPs in 3 genes (ACACA, FASN and ACLY) of DNL pathway were genotyped. Multivariate Cox proportional hazard regression model and Kaplan-Meier curve were used to analyze the association of SNPs with clinical outcomes. Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients. Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes. Moreover, patients carrying VV genotype in rs11871275 had decreased recurrence risk, while patients carrying variant genotype in rs4485435 of FASN gene had increased recurrence risk. Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence. SNPs in DNL genes may serve as independent prognostic markers for HCC patients after surgery.

No MeSH data available.


Related in: MedlinePlus

Survival curves of OS (A and B) and RFS (C and D) of HCC patients stratified by SNPs.Homozygous wild-type genotype, heterozygous genotype and homozygous variant genotype for rs7211875 was TT, TC, CC, respectively; for rs11871275 was AA, AT, TT, respectively; for rs4485435 was GG, GC, CC, respectively.
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f1: Survival curves of OS (A and B) and RFS (C and D) of HCC patients stratified by SNPs.Homozygous wild-type genotype, heterozygous genotype and homozygous variant genotype for rs7211875 was TT, TC, CC, respectively; for rs11871275 was AA, AT, TT, respectively; for rs4485435 was GG, GC, CC, respectively.

Mentions: We assessed the effects of 9 SNPs in three DNL pathway genes (ACACA, FASN and ACLY) on the death and recurrence in HCC patients using the multivariate cox regression model (Table 2). After adjusting for gender, age, HBsAg status, AFP level, TNM stage and differentiation, our data showed that SNPs rs7211875 and rs11871275 in ACACA gene were significantly associated with the death risk of HCC patients under recessive model (for rs7211875, HR = 2.13, 95% CI = 1.17–3.88; P = 0.01; for rs11871275, HR = 0.22, 95% CI = 0.06–0.91; P = 0.04). Adjusted survival curve showed similar results, indicating that HCC patients carrying the homozygous variant (CC) genotype in rs7211875 had significantly worse OS than those carrying the other genotypes (P = 0.01, Figure 1A), whereas patients with homozygous variant (TT) genotype in rs11871275 had better OS than those with other genotypes (P = 0.04, Figure 1B). Moreover, our data showed that TT genotype in rs11871275 of ACACA gene reduced the recurrence risk of HCC when compared to patients with AA and AT genotypes (HR = 0.41, 95% CI = 0.17–1.00; P = 0.05), whereas variant genotype (GC/CC) in rs4485435 of FASN gene was associated with increased recurrence risk, when compared to patients with GG genotype (HR = 1.32; 95% CI = 1.02–1.72, P = 0.03). Kaplan-Meier analysis confirmed these findings, showing that HCC patients carrying the TT genotype in rs11871275 had better OS than those carrying the other genotypes (P = 0.05, Figure 1C), while patients with GC/CC genotypes in rs4485435 trended to show worse OS than did those with GG genotype (P = 0.09, Figure 1D).


Genetic variants in de novo lipogenic pathway genes predict the prognosis of surgically-treated hepatocellular carcinoma.

Jiang H, Dai J, Huang X, Chen Y, Qu P, Li J, Yi C, Yang Y, Zhang K, Huang Q - Sci Rep (2015)

Survival curves of OS (A and B) and RFS (C and D) of HCC patients stratified by SNPs.Homozygous wild-type genotype, heterozygous genotype and homozygous variant genotype for rs7211875 was TT, TC, CC, respectively; for rs11871275 was AA, AT, TT, respectively; for rs4485435 was GG, GC, CC, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4379911&req=5

f1: Survival curves of OS (A and B) and RFS (C and D) of HCC patients stratified by SNPs.Homozygous wild-type genotype, heterozygous genotype and homozygous variant genotype for rs7211875 was TT, TC, CC, respectively; for rs11871275 was AA, AT, TT, respectively; for rs4485435 was GG, GC, CC, respectively.
Mentions: We assessed the effects of 9 SNPs in three DNL pathway genes (ACACA, FASN and ACLY) on the death and recurrence in HCC patients using the multivariate cox regression model (Table 2). After adjusting for gender, age, HBsAg status, AFP level, TNM stage and differentiation, our data showed that SNPs rs7211875 and rs11871275 in ACACA gene were significantly associated with the death risk of HCC patients under recessive model (for rs7211875, HR = 2.13, 95% CI = 1.17–3.88; P = 0.01; for rs11871275, HR = 0.22, 95% CI = 0.06–0.91; P = 0.04). Adjusted survival curve showed similar results, indicating that HCC patients carrying the homozygous variant (CC) genotype in rs7211875 had significantly worse OS than those carrying the other genotypes (P = 0.01, Figure 1A), whereas patients with homozygous variant (TT) genotype in rs11871275 had better OS than those with other genotypes (P = 0.04, Figure 1B). Moreover, our data showed that TT genotype in rs11871275 of ACACA gene reduced the recurrence risk of HCC when compared to patients with AA and AT genotypes (HR = 0.41, 95% CI = 0.17–1.00; P = 0.05), whereas variant genotype (GC/CC) in rs4485435 of FASN gene was associated with increased recurrence risk, when compared to patients with GG genotype (HR = 1.32; 95% CI = 1.02–1.72, P = 0.03). Kaplan-Meier analysis confirmed these findings, showing that HCC patients carrying the TT genotype in rs11871275 had better OS than those carrying the other genotypes (P = 0.05, Figure 1C), while patients with GC/CC genotypes in rs4485435 trended to show worse OS than did those with GG genotype (P = 0.09, Figure 1D).

Bottom Line: Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients.Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes.Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

ABSTRACT
Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. However, effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. A total of 492 primary HCC patients treated with surgery were included in this study. Nine SNPs in 3 genes (ACACA, FASN and ACLY) of DNL pathway were genotyped. Multivariate Cox proportional hazard regression model and Kaplan-Meier curve were used to analyze the association of SNPs with clinical outcomes. Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients. Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes. Moreover, patients carrying VV genotype in rs11871275 had decreased recurrence risk, while patients carrying variant genotype in rs4485435 of FASN gene had increased recurrence risk. Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence. SNPs in DNL genes may serve as independent prognostic markers for HCC patients after surgery.

No MeSH data available.


Related in: MedlinePlus