AI Article Synopsis
- The study investigates the impact of genetic variations (SNPs) in the Notch signaling pathway on survival rates of patients with esophageal squamous cell carcinoma (ESCC).
- Researchers analyzed data from 1,009 ESCC patients to identify associations between these SNPs and overall patient survival using advanced statistical methods.
- Findings indicate that specific SNPs in the HDAC9 gene are linked to poorer survival and could potentially be used as biomarkers, although further research is required to validate these results.
Article Abstract
Background: The Notch signaling pathway is involved in the progression of esophageal squamous cell carcinoma (ESCC), although the roles of single nucleotide polymorphisms (SNPs) of the Notch signaling pathway genes in the process remain unknown.
Methods: The present study included 1009 patients with histopathologically diagnosed ESCC at Fudan University Shanghai Cancer Center. Two-stage multivariate Cox proportional hazards regression analysis was used to estimate associations between 13,248 SNPs in 103 Notch signaling pathway genes and overall survival of the patients.
Results: We found that overall survival of the patients was significantly associated with genotypes of HDAC9 rs1729318 (AT+TT vs. AA: hazard ratio = 1.44, 95% confidence interval = 1.16-1.80, p = 0.001) and HDAC9 rs1339555498 (GT + TT vs. GG: hazard ratio = 1.38, 95% confidence interval = 1.10-1.74, p = 0.005). Further receiver operator characteristic (ROC) curve analysis indicated that the model with both available clinical factors and these two SNPs improved the area under the ROC curve compared to the model with clinical factors only (1-year: 0.66 vs. 0.64, p = 0.034). Additional expression quantitative trait loci analysis showed that the rs1729318 T variant genotypes were associated with increased mRNA expression levels of HDAC9 in normal esophageal muscular tissue (p = 0.003).
Conclusions: The results suggest that these two potential functional SNPs on HDAC9 may serve as biomarkers for predicting survival of ESCC patients. However, further studies are needed to confirm these findings.
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| http://dx.doi.org/10.1002/jgm.3438 | DOI Listing |
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