The new diagnosed cases and deaths of ovarian cancer will respectively be 22,240
and 14,070 in the United States. OC involves a heterogenous group of malignancies that differ from etiology, molecular biology, and other characteristics [2]. OC is the most common malignant tumor. High-risk ovarian carcinoma patients have very low cure rates, despite therapy comprised of combined treatments, including surgery, chemotherapy and radiation [2]. Clearly, identification of novel biomarkers and more effective therapies is extremely urgent.
LRH1 is a member of the nuclear receptor NR5A (Ftz-F1) subfamily which expresses in endodermal origin tissues containing the intestine, liver, exocrine pancreas [14], ovary [15–18], pre-adipocyte [19], and placenta [20]. Recent studies have reported that LRH1 protein functioned as a cancer regulator which exist in extensive procedures, such as cell proliferation, chemotherapy resistance, and tumor progress [6, 21, 22]. In the present study, we noticed that LRH1 protein expression showed high expression in OC tissues. Moreover, it indicated an increased trend of LRH1 protein and mRNA expression from T1 to T2 and its matched M. This study firstly identified overexpression of LRH1 in OC tissues. Preceding studies showed similar result in non-small cell lung cancer tissues and colon cancer tissues. Liu et al. [9] demonstrated that LRH1 was highly overexpressed in non-small cell lung cancer tissues compared with normal tissues. Wu et al. [8] carried out IHC in colon cancer tissues to test LRH1 expression, which indicated that comparing with the adjacent normal tissues, the protein level of LRH1 was outstandingly elevated in the cancerous tissues. Additionally, Jin et al. [10] verified LRH1 expression in three hepatoblastoma cell lines, HepG2, HuH6 and HepT1, and one control cell line, THLE-2 by western blotting and found that LRH1 expression was also remarkably upgraded in HepG2 cells and HuH6 cells. Thus, LRH1 may provide a candidate molecular marker for malignant behavior of tumor.
A number of studies have viewed LRH1 as a significant prognosis biomarker for tumor invasion and proliferation in several carcinomas, for example pancreases cancer [23]. Enlightened by these researches, we were prompted to identify the role of LRH1 overexpression as a predictor for clinicopathological and prognostic significance. We recognized that elevated LRH1 protein expression was tremendously corresponded with FIGO stages, lymph node metastasis and intraperitoneal metastasis. Furthermore, multivariate logistic regression model demonstrated that high standard of LRH1 expression was significantly associated with lymph node metastasis and intraperitoneal metastasis. In addition, the OS periods in patients with high LRH1 expression were shorter than that in patients with low LRH1 expression. Oppositely, patients whose LRH1 expression is low presented better prognoses than those with high LRH1 expression. Wang et al. [24] adopted bioinformatics analysis to screen on the focus of the nuclear receptor (NR) family. They found that overexpression of these orphan NRs could increase cancer stem cell markers expression and enhanced spheroid formation capacity in prostate cancer cells. Moreover, they concluded that LRH1 could be the potential therapeutic targets for PCSCs or castration-resistant prostate cancer.
The mechanism of LRH1 influencing tumorigenesis, cell proliferation, migration, chemotherapy resistance varies in different kinds of cancers. Our study showed that LRH1 down-regulation inhibited OC cells proliferation and migration in vitro. In pancreases cancer, Lin et al. [7] have demonstrated that LRH1 enhanced transcriptional activity of β-catenin and up-regulated the expression of downstream target genes (c-Myc, MMP2/9), thus promoted migration and invasion. In breast cancer, it has found that MDC1 transcription was promoted by LRH1 through directly activating MDC1 promoter and resulting in elevated γH2AX levels. Furthermore, the mRNA level of LRH1 and MDC1 were positively correlated in recurrent breast cancer samples. In addition, LRH1 promoted breast cancer cell chemoresistance by enhancing the expression of MDC1 and attenuating DNA damage [6]. All of these findings suggest an important biological role of LRH1 in carcinogenesis and tumor progression.