Fibroblast growth factor receptor 4 (FGFR4) has been confirmed to be associated with the progression and prognosis of ovarian cancer, while the underlying mechanism has not been well elucidated and the clinical significance of its ligand, fibroblast growth factor 19 (FGF19), has not been explored. To study the clinical significance of FGF19 in advanced‑stage serous ovarian cancer, we detected the expression of FGF19 and FGFR4 by immunohistochemistry (IHC), evaluated the correlation between FGF19 and clinicopathological factors by Chi-square (χ2) test, and analyzed the association between FGF19, FGFR4 and the overall survival rate using the Kaplan‑Meier method. As a result, we demonstrated that high expression of FGF19 and FGFR4 both predicted unfavorable prognosis (P=0.033 and 0.018, respectively), whereas FGF19-FGFR4 double high expression was a more sensitive prognostic factor of advanced-stage serous ovarian cancer (P<0.001). With experiments in vitro, we demonstrated that both recombinant FGF19 and secreted FGF19 promoted ovarian cancer proliferation and invasion by activating FGFR4 and the subsequent AKT-MAPK signaling pathway, suggesting that FGF19-FGFR4 signaling may auto-activate in a paracrine or autocrine manner. In conclusion, FGF19-FGFR4 double high expression was a more sensitive prognostic factor than FGF19 or FGFR4 alone in advanced-stage serous ovarian cancer. The FGF19-FGFR4 signaling pathway can promote ovarian cancer proliferation and invasion by the AKT-MAPK signaling pathway, indicating that FGF19 could be a potential therapeutic drug target of advanced-stage serous ovarian cancer.

In the present study, we explored the participation of Notch1 targeted regulation of mir-224/LRIG2 gene signal pathway in proliferation and apoptosis of cervical cancer cells. Forty-nine cases of cervical cancer lesion samples from cervical cancer patients treated in our hospital from February 2013 to February 2015 were chosen as subjects (the observation group), and cervical samples of healthy women (42 cases) during the same period were used as the control group. We determined the mRNA and protein expression of Notch1, mir-224, and LRIG2 genes. We also analyzed the mutual relationship between Notch1 gene expression and cervical cancer. The Notch1 genes in the cervical cancer cells (HeLa) were silenced and overexpressed to measure cancer apoptosis with flow cytometry. After obstruction of the Notch1 signal pathway, the mRNA and protein expression in the mir-224 and LRIG2 genes was also measured. It was found that in comparison to the control group, Notch1 gene expression in the observation group was significantly higher (p<0.05), cell growth was suppressed in Notch1 silent cell strains but accelerated in overexpressed Notch1 cells. The silencing of Notch1 genes can lead to the reduction of mir-224/LRIG gene and protein levels, while overexpression of the Notch1 genes increased the mir-224/LRIG gene and protein levels. In conclusion, the Notch1 gene is positively related to cervical cancer and can promote the occurrence of the disease. The potential mechanism shows that Notch1 gene can regulate cervical cancer cell proliferation by regulating the mir-224/LRIG2 signal pathway.

Abstract. The effects of platinum-based drugs are controlled by genes that are involved in DNA detoxification, including glutathione S-transferase (GST)P1 and GSTM1, which have been associated with increased benefits in the chemotherapeutic treatment of patients with ovarian cancer. The present study assessed the effect of single nucleotide polymorphisms in GST genes on the overall survival (OS) of patients with ovarian serous cystadenocarcinoma that were treated with chemotherapy. A total of 95 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms in the patients were genotyped using the following methods: Pyrosequencing, to identify GSTP1 Ile105Val; a relative quantification method, to identify the copy number variation in GSTM1; and polymerase chain reaction followed by gel electrophoresis, to identify the null vs. non-null genotypes of GSTM1. The association between genotypes and OS of patients was assessed using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. The OS of patients treated with paclitaxel + carboplatin-based chemotherapy was significantly increased, compared with patients treated with alternative forms of chemotherapy (P= 0.035). The OS of patients did not differ significantly between different GSTP1 genotypes (log-rank test, P=0.17). Cox proportional hazards regression analysis revealed that, since the start of the treatment, there was not a significant association between the GSTP1 isoleucine allele and the OS for heterozygous carriers of the isoleucine allele [hazards ratio (HR), 1.78; 95% confidence interval (CI), 0.77-4.12; P=0.18] and no homozygous carriers of the valine allele had been detected (HR, 0.00). There was no significant difference between GSTM1 genotypes, according to Kaplan-Meier survival analysis (log-rank test, P=0.83). Patients that possessed ≤1 copy of GSTM1 exhibited no decrease in OS (HR, 0.96; 95% CI, 0.37-2.51; P=0.94), compared with patients that possessed two copies of GSTM1 (HR, 0.71; 95% CI, 0.22-2.28; P=0.56). Overall, the present results suggest that there are no associations between polymorphisms in the GSTP1 and GSTM1 genes and the OS of patients with ovarian cancer following administration of adjuvant chemotherapy.