Abstract
BackgroundLiver receptor homolog 1 (LRH1) plays a vital role in several human cancers, but its role in ovarian cancer (OC) remains unclear. We aimed to explore the functions of LRH1 and its clinical relevance.MethodsLRH1 expression was evaluated by immunohistochemistry and reverse transcription quantitative polymerase chain reaction (RT-qPCR). The effects of LRH1 on tumor cell proliferation, migration and epithelial–mesenchymal transition (EMT) were evaluated in vitro. Furthermore, bioinformatics analysis was applied to predict the functions of LRH1.ResultsRT-qPCR showed that LRH1 mRNA expression was higher in the invasive lesions (P < 0.05). LRH1 overexpression was extremely related with elevated International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.001), lymph node metastasis (P = 0.011), peritoneal metastasis (P = 0.001), and platinum resistance (P = 0.037). Furthermore, LRH1 expression was an independent prognostic index for disease-free survival in patients with OC (P = 0.041). LRH1 overexpression (P = 0.011), FIGO stage (P < 0.001), and ascites (P = 0.015) independently affected peritoneal metastasis in patients with OC. LRH1 knockdown significantly inhibited the proliferation, migration, and EMT of human OC cells (P < 0.05); however, it reversed cisplatin resistance. Bioinformatics analysis indicated that the functions of LRH1 were associated with the PRC1 complex, nuclear ubiquitin ligase complex, and Polycomb-group (PcG) proteins.ConclusionsThis study provides evidence of the predictive value of LRH1 on peritoneal metastasis and poor outcome and highlights the potential role of LRH1 as a biomarker for the targeted therapy of OC. Furthermore, LRH1 promotes OC cell proliferation, migration, and EMT in vitro, and its functions may be associated with PRC1 complex, nuclear ubiquitin ligase complex, and PcG proteins.
Highlights
Liver receptor homolog 1 (LRH1) plays a vital role in several human cancers, but its role in ovarian cancer (OC) remains unclear
reverse transcription (RT)-qPCR was carried out to determine the difference in the LRH1 mRNA expression between Ovarian cancer (OC) and normal ovarian tissues (Figure 1)
No discrepancy was observed in the LRH1 mRNA expression between normal tissues and OC tissues without metastasis (T1) (P > 0.05)
Summary
Liver receptor homolog 1 (LRH1) plays a vital role in several human cancers, but its role in ovarian cancer (OC) remains unclear. We aimed to explore the functions of LRH1 and its clinical relevance. Ovarian cancer (OC) is the most lethal gynecologic malignancy among women. An estimate of 21,750 new cases of OC will be diagnosed, and 13,940 women will die of OC in the United States in 2020 according to the American Cancer Society [1]. ADP ribose polymerase inhibitors (PARPs) used in the management of epithelial ovarian cancer (EOC) have renewed the hope of patients with EOC. The prognosis for the advanced stage of OC remains poor even though a novel technology has been applied for the diagnosis and treatment of OC [9]. The identification of an ideal biological factor that predicts the malignant biological behavior and prognosis of OC will be helpful
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