Identification of candidate susceptible genes associated with ovarian clear cell carcinoma using cis-eQTL analysis = Identification of candidate susceptible genes associated with ovarian clear cell carcinoma using cis-eQTL analysis

다국어 초록 (Multilingual Abstract)

Objective: Ovarian clear cell adenocarcinoma (Ov-CCA)has a significant ethnic difference between Western populations and Japanese. Understanding of specific genetic alterations which associated with ethnic differences could lead to understanding of pathogenesis in Ov-CCA. The purpose of this study is to investigate the single nucleotide polymorphisms (SNPs) and the associated genes which correlated with the Japanese Ov-CCA using expression quantitative trait loci (eQTL) analysis with the publicly available datasets.
Methods: The differences of genotype between three races (Western, Chinese, and Japanese) were compared using eQTLs analysis with the HapMap3 and the 1000 genome project datasets. 4 SNPs and 7 associated genes were identified. To evaluating the clinical significance of 7 identified genes in clear cell histology, the survival analysis according to the gene expression were perfomred with kidney renal clear cell carcinoma (KIRC) and high grade serous ovarian carcinoma (HGSOC) datasets in TCGA database.
Results: Of the 935 identified cis-eQTLs, 4 SNPs (rs4873815, rs12976454, rs11136002, and rs13259097) had the different frequencies of alternative allele among Western, Chinese and Japanese with statistically significant (all p < 0.001) and these 4 SNPs were associated with 7 transcripts (APBA3, C8orf58, KIAA1967, NAPRT1, RHOBTB2, TNFRSF10B and ZNF707). To investigate the clinical significance, survival analysis was done using TCGA dataset and the expressions of the 3 genes (ZNF707, TNFRSF10B and RHOBTB2) were correlated with overall survival in KIRC (p < 0.001, p < 0.001 and p = 0.007) which were not shown in HGSOC.
Conclusion: In this study, we identified that the expression of ZNF707, TNFRSF10B and RHOBTB2 were correlated with overall survival in clear cell histology although the KIRC dataset were used. eQTL analysis using the publicly available datasets may facilitate the discovery of novel genetic alteration in Ov-CCA and provide the basis for the understanding of Ov-CCA pathogenesis.