Identification of Candidate Genes Associated with Susceptibility to Ovarian Clear Cell Adenocarcinoma Using cis-eQTL Analysis

Ovarian clear cell adenocarcinoma (Ov-CCA) has a higher prevalence in the Japanese ancestry than other populations. The ancestral disparities in Ov-CCA prevalence suggests the presence of Ov-CCA-specific genetic alterations and may provide an opportunity to identify the novel genes associated with Ov-CCA tumorigenesis. Using 94 previously reported genes as the phenotypic trait, we conducted multistep expression quantitative trait loci (eQTL) analysis with the HapMap3 project datasets. Four single-nucleotide polymorphisms (SNPs) (rs4873815, rs12976454, rs11136002, and rs13259097) that had different allele frequencies in the Japanese ancestry and seven genes associated in cis (APBA3, C8orf58, KIAA1967, NAPRT1, RHOBTB2, TNFRSF10B, and ZNF707) were identified. In silico functional annotation analysis and in vitro promoter assay validated the regulatory effect of rs4873815-TT on ZNF707 and rs11136002-TT on TNFRSF10B. Furthermore, ZNF707 was highly expressed in Ov-CCA and had a negative prognostic value in disease recurrence in our sample cohort. This prognostic power was consistently observed in The Cancer Genome Atlas (TCGA) clear cell renal cell carcinoma dataset, suggesting that ZNF707 may have prognostic value in clear cell histology regardless of tissue origin. In conclusion, rs4873815-TT/ZNF707 may have clinical significance in the prognosis and tumorigenesis of Ov-CCA, which may be more relevant to clear cell histology. Besides, this study may underpin the evidence that cis-eQTL analysis based on ancestral disparities can facilitate the discovery of causal genetic alterations in complex diseases, such as cancer.

Low Expression of S100P Is Associated With Poor Prognosis in Patients With Clear Cell Adenocarcinoma of the Ovary

ObjectiveThe S100P protein stimulates cell proliferation and survival, thereby contributing to cancer progression. The purposes of this study were to evaluate S100P expression in ovarian clear cell adenocarcinoma and to determine whether S100P expression was correlated with the clinicopathological features or prognoses of patients with clear cell adenocarcinoma.MethodsWe examined S100P expression in 30 ovarian clear cell adenocarcinoma specimens using immunohistochemistry analysis. The Kaplan-Meier method was used for analysis of overall survival, and comparisons were made based on the log-rank test.ResultsNegative staining for nuclear S100P was associated with a poor prognosis as compared with that of positive staining for nuclear S100P in specimens from patients with clear cell adenocarcinoma.ConclusionsThese data suggested that S100P may serve as an independent prognostic factor and marker for acquired resistance to chemotherapeutic drugs in clear cell adenocarcinoma.