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- Title
Potentially functional genetic variants in ferroptosisrelated CREB3 and GALNT14 genes predict survival of hepatitis B virus-related hepatocellular carcinoma.
- Authors
Shicheng Zhan; Moqin Qiu; Xueyan Wei; Junjie Wei; Liming Qin; Binbin Jiang; Qiuping Wen; Peiqin Chen; Qiuling Lin; Xiaoxia Wei; Zihan Zhou; Yanji Jiang; Xiumei Liang; Runwei Li; Yingchun Liu; Hongping Yu
- Abstract
Background: Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis-related genes on survival in hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) patients remains unknown. Methods: We used two-stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosisrelated genes and overall survival (OS) of 866 HBV-HCC patients. Results: We identified that two potentially functional SNPs (CREB3 rs10814274 C>T and GALNT14 rs17010547 T>C) were significantly independently associated with the OS of HBV-HCC patients (CT+TT verse CC, hazards ratio (HR)=0.77, 95% confidence interval (CI)=0.67–0.89, p<0.001 for rs10814274 and TC+CC verse TT, HR=0.66, 95% CI=0.53–0.82, p<0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1–2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR=0.56, 95% CI=0.45– 0.70, p<0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival-associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells. Conclusion: These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV-HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings.
- Subjects
GENETIC variation; LOCUS (Genetics); SINGLE nucleotide polymorphisms; HEPATOCELLULAR carcinoma; HEPATITIS B; SEROCONVERSION
- Publication
Cancer Medicine, 2024, Vol 13, Issue 1, p1
- ISSN
2045-7634
- Publication type
Article
- DOI
10.1002/cam4.6848