RESUMO
Background: Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE). Method: The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs). Results: MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI = 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity. Conclusions: These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.
RESUMO
RIT1, (Ras-like without CAAX1), the founding member of a novel branch of the Ras subfamily, mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation, and it may play crucial oncogenic role in human cancer. The purpose of the current study was to characterize the expression pattern of RIT1 and assess the clinical significance of RIT1 expression in endometrial cancer patients. The mRNA and protein expression of RIT1 was significantly overexpressed in 7 endometrial cancer cell lines by qPCR and Western blot, respectively. In addition, RIT1 mRNA expression was elevated in 36 freshly frozen endometrial cancer tissues compared to 21 non-cancerous endometrial tissue samples. Similar results were observed by analyzing GEO datasets. Immunohistochemistry was used to examine the protein expression of RIT1 in two tissue microarrays containing 257 cases of tumor and 31 non-tumor tissues, which showed that elevated expression of RIT1 was significantly correlated with pathological type, clinical stage, grade and vascular invasion. Importantly, Kaplan-Meier survival analysis indicated that RIT1 expression was associated with overall survival of endometrial cancer patients. Multivariate Cox regression analysis revealed that RIT1 expression was one of the independent prognostic factors for endometrial cancer patients. Furthermore, RIT1 combined with other clinicopathological risk factors was a more significant model in ROC curve comparison. In conclusion, elevated expression of RIT1 may contribute to the progression of endometrial cancer and thus may serve as a novel prognostic marker and a promising molecular target for the treatment of endometrial cancer.
Assuntos
Carcinoma/metabolismo , Neoplasias do Endométrio/metabolismo , Proteínas ras/metabolismo , Adulto , Carcinoma/genética , Carcinoma/mortalidade , Carcinoma/patologia , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Progressão da Doença , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Proteínas ras/genéticaRESUMO
BACKGROUND/AIMS: To investigate cytotrophoblast (CTB) invasive ability and human uterine spiral artery smooth muscle cell (HUSASMC) apoptosis in a coculture model with serum from preeclamptic pregnancies. METHODS: Transwell migration assay was used to detect the invasive ability of CTBs. Cocultured CTBs and HUSASMCs were incubated with normal or preeclamptic serum for 24 h. Monocultures of CTBs and HUSASMCs were treated identically to the cocultures and served as controls. HUSASMC viability and apoptosis rates were determined by MTT and annexin V-FITC assays. The expressions of Fas ligand (FasL) mRNA in CTBs and Fas mRNA in HUSASMCs were detected by RT-PCR. The expression of the Fas protein in HUSASMCs was detected by Western blotting. RESULTS: In a model of CTBs cocultured with HUSASMCs, preeclamptic serum effectively decreased the invasive ability and FasL mRNA expression of the CTBs. Preeclampsia serum also increased HUSASMC viability, decreased their apoptotic rate, and decreased the expression of Fas mRNA and protein. CONCLUSION: The abnormal invasive ability of CTBs and decreased expression of the Fas/FasL system may be directly involved in the defective remodeling of the uterine spiral arteries during preeclampsia. Furthermore, the decrease in HUSASMC apoptosis may be related to the abnormal expression of Fas/FasL.