ArticleMolecular genetics & genomic medicine2026
Prognostic Impact of ERAP1 Genetic Variants and Haplotypes in Cervical Cancer: Insights From TCGA-CESC and a Brazilian Patient Cohort.
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Abstract
backgroundThis study aimed to evaluate the association between genetic variants and haplotypes of ERAP1 and clinical outcomes in cervical cancer patients, utilizing data from the TCGA-CESC and a cohort of Brazilian patients.
methodsERAP1 variants and haplotypes were evaluated in two distinct cohorts: whole-exome sequencing (WES) data from 173 cervical cancer cases in the TCGA-CESC dataset, and Sanger sequencing data from 52 Brazilian cervical cancer patients. The TCGA-CESC data were employed for in silico analysis to identify significant ERAP1 variants and haplotypes, which were subsequently evaluated in Brazilian cervical cancer samples. The Tumor IMmune Estimation Resource (TIMER) tool was used to assess the association between ERAP1 expression and immune cell infiltration.
resultsHaplotype analysis of ERAP1 in the TCGA-CESC dataset revealed that H005 (rs26653-rs2287987-rs30187-rs10050860-rs17482078-rs27044) and H023 (rs26653-rs27895-rs30187-rs27044) haplotypes were significantly associated with poorer survival outcomes. Homozygosity for H005 and the presence of H023 were strongly associated with both overall survival (OS) (HR = 9.591, p = 0.00384; HR = 10.183, p = 0.02862, respectively) and disease-specific survival (DSS) (HR = 12.851, p = 0.00162; HR = 15.183, p = 0.01191, respectively). TCGA-CESC data showed that homozygosity for rs2287987 (p.Met349Val) was associated with an increased risk of death in both overall survival (OS) (HR = 11.043, p = 0.00376) and disease-specific survival (DSS) (HR = 13.833, p = 0.00255), whereas rs30187 (p.Lys528Arg) demonstrated a protective effect for DSS, reducing mortality risk in both heterozygous (HR = 0.374, p = 0.04055) and homozygous (HR = 0.346, p = 0.03845) forms. However, although these variants were individually associated with survival outcomes in the dataset, this association was not retained in the multivariate analysis, suggesting that these variants may not have an independent prognostic effect. Similarly, no associations were found for these variants in the Brazilian cervical cancer cohort, suggesting that the impact of these variants on the prognosis of cervical cancer patients may be primarily influenced by the combination of variants. Furthermore, ERAP1 expression levels were positively correlated with CD8
conclusionERAP1 haplotype H005 homozygosity and the presence of H023 were linked to poorer prognosis, indicating their potential as prognostic biomarkers in cervical cancer patients. Individually, the rs2287987 variant showed a potential association with worse outcomes in the TCGA dataset; however, this finding was not replicated among Brazilian patients, suggesting the potential role of these variants when considered as haplotypes in the function of ERAP1. Additionally, the protective role of CD8+ T cell infiltration highlights its relevance as a possible therapeutic target for improving survival in cervical cancer patients.
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