Identification of candidate genes associated with tubal origin of high-grade serous ovarian cancer.

Abstract

Evidence indicates that high-grade serous ovarian carcinoma arises from the fallopian tube, rather than ovarian surface epithelium. This is termed the ‘tubal origin’ theory. The aim of the present study was to compare the immunophenotype and gene expression profiling among high-grade serous ovarian carcinoma (HGSOC), fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) based on tubal origin theory, and identify the differential genes associated with ovarian carcinogenesis. A total of 61 cases of fresh tissue samples including 21 cases of HGSOC, 20 cases of OSE, and 20 cases of FTE were obtained following surgical resection. Immunostaining was performed to detect the expression of PAX8, which has been considered as a potential immunophenotype marker of Müllerian origin. Illumina BeadChip was applied for gene expression profiling. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the differential expression of candidate genes between HGSOC and FTE. The results of the present study demonstrated that PAX8 was highly expressed in HGSOC (19/21, 90.4%) and FTE (20/20, 100%), but not in OSE (3/20, 14.3%). A dendrogram generated by cluster analysis indicated a higher similarity of gene expression profile between HGSOC and FTE than OSE. A total of 2,412 differentially expressed genes were identified (absolute fold change >2) between HGSOC and FTE, including 822 upregulated genes in cancer and 1,590 downregulated genes. S100 calcium binding protein P, Ras-interacting protein 1, Wnt family member 5A, tumor-associated calcium signal transducer 2, Dickkopf Wnt signaling pathway inhibitor 3 and tumor suppressor candidate 3 genes were identified as candidate markers, of which the differential gene expression in HGSOC and FTE was confirmed by RT-qPCR (P<0.05). The results indicate the presence of a greater similarity in the immunophenotype and gene expression profile of HGSOC and FTE, when compared with OSE, which was consistent with the tubal origin theory of HGSOC.