Differential expression of stem cell related genes in endometrial and ovarian carcinoma

Abstract

In the embryonic stem cells, germ cells, and adult stem cells, a cascade of ‘stem-cell related’ genes are being activated or inactivated to determine whether the cells will adopt a proliferative or differentiated fate. Previous studies postulated that cancer cells share common characteristics with stem cells and there is relationship between oncogenesis and embryogenesis. Moreover, recent evidence demonstrated that solid tumors harbored a population of cancer stem cells. We are particularly interested in the role of these stem-cell related genes in gynecologic cancers, especially endometrial adenocarcinoma (EmCA) and ovarian carcinoma (OvCA), being the most common and the most fatal cancers of the female genital tract, respectively. In this study, we aim to determine the level of mRNA expression of stem cell-related genes OCT4, STAT3, SOX2, NANOG, and FOXD3 in endometrial and ovarian carcinoma by quantitative real-time reverse-transcription polymerase chain reactions (RT-PCR) using 5’ nuclease assay. RNA was extracted from fresh frozen tissues of 40 endometrial carcinoma including 32 cases of endometrioid type, and eight cases of non-endometrioid type such as high grade papillary serous and clear cell carcinoma; as well as 37 ovarian carcinoma including 12 serous type, 10 endometrioid type, nine mucinous type, and six clear cell type. The non-tumor tissue of the same patients, usually the Fallopian tube was also retrieved for comparison. The RNA was reversely transcribed and the expression level of each of the stem cell related genes in cancer and non-tumor samples of each case was normalized with that of the housekeeping gene GAPDH and compared. Our results showed that the endometrial and ovarian carcinoma share the same expression pattern of these genes. In general, the expression of STAT3, SOX2, NANOG, and FOXD3 was lower in the cancer samples compared with normal tissue whilst the OCT4 expression was higher in the cancers, reaching statistical significance in STAT3 (p<0.0001 and 0.0013 for OvCA and EmCA respectively, Wilcoxon paired signed-rank test), SOX2 (<0.0001 for EmCA), NANOG (p=0.0002 and <0.0001 for OvCA and EmCA respectively) and FOXD3 (p= 0.0016 and <0.0001 for OvCA and EmCA respectively), and OCT4 (0.0028 for EmCA). There was statistically significant correlation in the expression patterns of OCT4, STAT3, SOX2, NANOG, and FOXD3 in both endometrial (p<0.0001, Kruskal-Wallis Test) and ovarian (p=0.0036) carcinomas. Moreover, the expression of OCT4 was inversely correlated with histological grading of EmCA. To conclude, these five stem cell related genes may be involved in the pathogenesis of these cancers, and OCT4 in particular, is probably more important in the early stage of carcinogenesis.