RESUMEN
The utility of placental growth factor (PlGF) and its receptor VEGFR-1 (Flt-1) as biomarkers for cervical cancer has not been clarified yet. To address this issue, we investigated the levels of soluble PlGF (sPlGF) and soluble Flt-1 (sFlt-1) in the serum from patients with early cervical cancer, cervical intraepithelial neoplasia (CIN) and controls in this study. sPlGF and sFlt-1 were detected in 44 preoperative patients with cervical cancer, 18 cases with CIN, and 20 controls by ELISA. It was found that both sPlGF and sFlt-1 were significantly increased in the cervical cancer group as compared with those in CIN and control groups. sPlGF presented a high diagnostic ability of cervical cancer, with a sensitivity of 61.36% and a specificity of 89.47%; and sFlt-1 with a sensitivity of 50.00% and a specificity of 92.11%. Importantly, the combined use of sPlGF and sFlt-1 could increase the diagnostic rate of cervical cancer, with a sensitivity of 70.45% and a specificity of 92.11%. These results indicated that both sPlGF and sFlt-1 in circulation can serve as possible valuable diagnostic biomarkers for cervical cancer, and the combined use of them can be more valuable to diagnose the patients with early cervical cancer.
Asunto(s)
Detección Precoz del Cáncer , Factor de Crecimiento Placentario/sangre , Neoplasias del Cuello Uterino/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Biomarcadores de Tumor/sangre , Femenino , Humanos , Proteínas de la Membrana , Persona de Mediana Edad , Células Neoplásicas Circulantes/patología , Embarazo , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
OBJECTIVE: To assess roles of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in the mechanisms of lymphangiogenesis in epithelial ovarian carcinoma. METHODS: (1) Expression of Prox1, a newly described lymphatic endothelial cell nucleus marker, VEGF-A, VEGF-C, VEGF-D and PDGF-A, PDGF-B, PDGF-C, PDGF-D were detected by RT-PCR in SKOV3 cell line and in 90 ovarian tissue samples, included 15 benign tumors, 10 borderline tumors, 45 malignant tumors and 20 normal ovarian samples. (2) Expression levels of Prox1, VEGF-A, -C, -D and PDGF-A, -B, -C, -D were detected in 90 ovarian tissue sample mentioned above by real-time quantitative PCR (RTQ-PCR). RESULTS: (1) Prox1 was expressed in ovarian samples mentioned above, while not detected in SKOV3 cell. VEGF-A, -C, -D and PDGF-A, -B, -C, -D were found in SKOV3 cell and various ovarian tissues. (2) Expression levels of Prox1 (2.2 +/- 1.3, P < 0.01), VEGF-A (3.5 +/- 1.5, P < 0.01), VEGF-C (19 +/- 14, P < 0.01), VEGF-D (3.0 +/- 1.8, P < 0.01) and PDGF-A (3.3 +/- 3.3, P < 0.05), PDGF-C (6.9 +/- 4.6, P < 0.01) in malignant group were found to be significantly higher than those in borderline group and benign group. (3) The expression levels of Prox1, VEGF-A and PDGF-A were significantly greater in samples from the patients with lymph node metastasis (Prox1: 3.0 +/- 1.4, VEGF-A: 4.1 +/- 1.7, PDGF-A: 4.9 +/- 4.1), peritoneum metastasis (Prox1: 2.8 +/- 0.9, VEGF-A: 4.0 +/- 1.8, PDGF-A: 4.5 +/- 4.0) and in stage III - IV (Prox1: 2.6 +/- 1.3, VEGF-A: 4.0 +/- 1.4, PDGF-A: 4.1 +/- 3.7) than those without lymph node metastasis, without peritoneum metastasis and in stage I - II. There was a significant increased in the degree of VEGF-C and VEGF-D expression in positive lymph node metastasis group (VEGF-C: 24 +/- 13, VEGF-D: 3.9 +/- 2.0) compared with negative group (P < 0.05). (4) There were significant positive correlations between the expression levels of Prox1 and VEGF-D (r = 0.62, P < 0.01), PDGF-C (r = 0.91, P < 0.01) or PDGF-D (r = 0.61, P < 0.01). CONCLUSIONS: VEGF-A, VEGF-C and PDGF-A may promote lymphatic metastasis in epithelial ovarian carcinoma through else mechanisms other than lymphangiogenesis. VEGF-D may facilitate lymphangiogenesis and lymph node metastasis in epithelial ovarian cancer. There is no significant correlation between the expression of PDGF-B and lymphangiogenesis and lymph node metastasis. PCGF-C and PDGF-D may motivate lymphangiogenesis, but could not participate in lymph node metastasis in ovarian carcinoma.
Asunto(s)
Linfangiogénesis , Factor A de Crecimiento Endotelial Vascular , Humanos , Metástasis Linfática , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor C de Crecimiento Endotelial Vascular , Factor D de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Tumor cells need large energy and nucleic acids to proliferate and grow. For most of their energy needs, cancer cells depend more on glycolysis. For most of their nucleic acids needs, cancer cells depend more on the nonoxidative pathway of the pentose phosphate pathway. Transketolase(TKT) is a crucial enzyme in the nonoxidative pathway of the PPP. METHODS: The real-time quantity PCR was used to determine the expression of transketolase gene family in uterine cervix cancer. Transketolase activity of cell was determined by using enzyme-linked method. Cell proliferation was detected by using MTT. RESULTS: The TKTL1 mRNA was specifically over-expressed in uterine cervix cancer cells(HeLa cell line) compare with normal human endocervical epithelial cells(End1/E6E7 cell line)(P < 0.05), whereas the expression of TKT and transketolase-like gene 2(TKTL2) have no significant differences between the two cell lines(P > 0.05). Moreover, we found that total transketolase activity was significantly reduced, and cell proliferation was remarkably inhibited after anti-TKTL1 siRNA treatment in HeLa cells. The total transketolase activity and cell proliferation have no significant differences after anti-TKTL1 siRNA treatment in End1/E6E7 cells. CONCLUSION: These results indicate that TKTL1 plays an important role in total transketolase activity and cells proliferation in uterine cervix cancer.