Expression Of Opn And HIF-1α And Relationship Between OPN、HIF-1α And Radiotherapy And Chemotherapy Sensitivity In Cervical Cancer By TCM Syndrome Differentiations

ObjectiveThe purpose of this study is to investigate the expression of osteopontin and hypoxia inducible factor-1α, and the relationship of clinicopathologi-cal features in cervical cancer, and explore their correlation with radiother-apy and chemotherapy sensitivity of cervical cancer, then analysis the possibility of OPN and HIF-1α as predictors of radiotherapy and chemotherapy sensitivity in cervical cancer. Meanwhile detect the expression of OPN in serum level and the different expression before and after radiotherapy and chemotherapy, then investigate the possibility of the serum level of OPN as a predictor of radiotherapy and chemotherapy sensitivity in cervical cancer. And analysis the expression of OPN and HIF-1a in cervical cancer tissue and their relationship with Traditional Chinese Medicine. Therefore to provide new ideas for cervical cancer in integrative medicine.MethodsThe expression of OPN mRNA与HIF-1α mRNA in cervical cancer tissues were detected by real-time fluorescence quantitative PCR in49cases women with cervicalcancer,28cases of women with normal cervix from May2011to April2012. The level of osteopontin in serum from83cases of women with cervical cancers,48cases of women with normal cervical from March2009to April2012, was detected by enzyme-linked immunosorbent assay(ELISA). Analysis the expression of OPN and HIF-1α in cervical cancer and the levels of them pre-and post-treatment of radiotherapy and chemotherapy. Explore the role of OPN、 HIF-1α in the occurrence and development of cervical cancer, and theri relationship with radiotherapy and chemotherapy sensitivity;investigate the possibility of the serum level of OPN as a predictor of radiotherapy and chemotherapy sensitivity in cervical cancer. In this study, we also use TCM syndrome differentiation to analysis the expression level of OPN mRNA and HIF-1a mRNA in cervical cancer, and then explore the relationship between OPN mRNA、HIF-1α mRNA and TCM.Results1. The expression level of OPN mRNA and HIF-1a mRNA in the49cases of cervix cancer patiernts before treatment were significantly higher than the28cases of patients with normal cervical, The relative quantitative results were (5.534±0.752、4.624±0.408), the differences of statistic were significantly (p<0.05). The expression of OPN mRNA and HIF-1α mRNA in tissue of cervical cancer patients before treatment were related to the FIGO clinical stage, cytology classification, tumor invasive depth and lymph node metastasis:the levels of OPN mRNA and HIF-1a mRNA in Ⅲ～Ⅳ stage patients were higher than that in Ⅰ～Ⅱ stage patients, cytology classification was low-differentiated higher than moderately or well-differentiated;tumor invasive depth over1/2interstitial higher than less than1/2interstitial, significantly higher levels were associated with lymph node metastases(p<0.05). There was no significantly difference in different age and tissue types of the patients(p>0.05).2. Compared the expression levels of OPN mRNA and HIF-1a mRNA in20cases of cervical cancer patients with treatment of neoadjuvant chemotherapy, the expression levels of OPN mRNA and HIF-1α mRNA decreased significantly after neoadjuvant chemotherapy; the relative quantitative results of OPN mRNA and HIF-1a mRNA were (2.175±0.663.2.610±0.935), the statistical difference was significant(p<0.05).3. Compared with the effective group and the ineffective group of Neoadjuvant Chemotherapy, the expression levels of OPN mRNA and HIF-1α mRNA in effective group were decreased significantly after neoadjuvant chemotherapy (p<0.05),While in the uneffective group, there was no significant difference of the expression levels of OPN mRNA and HIF-1αmRNA before and after neoadjuvant chemotherapy (p>0.05).Compared with the expression levels of OPN mRNA and HIF-1α mRNA before neoadjuvant chemotherapy between effective group and the ineffective group, the effective group was lower than the ineffective group (p=0.016, p=0.001). Compared with the expression levels of OPN mRNA and HIF-1a mRNA after neoadjuvant chemotherapy between effective group and the ineffective group, the effective group was also lower than the ineffective group (p<0.05)4. The expressions of OPN mRNA and HIF-1α mRNA before neoadjuvant chemothe-rapy of cervical cancer were positively correlated with three Dultrasound parameters VI(angiogenesis index), FI(flow index),residualtumor volume percentage(residualtumor volume percentage=residualtumor volume/pretreat ment tumor volume X100%)(p<0.05). There were no significant correlation with VFI(blood flow index) and the tumor volume before chemotherapy (p>0.05)5. The relative quantitative results of OPN mRNA and HIF-1α mRNA in cervical cancer patients of pre-and post-neoadjuvant chemotherapy, were closely related with clinicopathological features:Squamous cell carcinoma patients was significantly higher than patients with adenocarcinoma (p=0.026, p=0.023); Cytology classification is low-differentiated patients lower than moderately or well-differentiated patients (p=0.021, p=0.036); tumor invasive depth less than1/2interstitial patients higher than over1/2interstitial patients (p=0.015, p=0.018); with lymph node metastasis was significantly lower than those without lymph node metastasis(p<0.05).There was no significantly difference with patient age and clinical stage (p>0.05)6. The influencing sensitivity factors of neoadjuvant chemotherapy by Logistic regression analysis showed that:the expression level of OPNmRNA and HIF-1α mRNA before neoadjuvant chemotherapy,the ultrasonic parameters VI and Fl, which were closely related with neoadjuvant chemotherapy sensitivity. The OR values of them were respectively5.604,5.056,3.943,4.337, the statistical difference was significantly (p<0.05).7. The expression levels of OPN mRNA and HIF-1α mRNA in10cases of cervical cancer patients were significantly decreased after treatment of concurrent chemoradiotherapy. The relative quantitative results were (7.710±0.575 4.518±0.390), there were significantly statistical differences(p<0.05).8. There were closely relationships between OPN mRNA and HIF-1α mRNA expressions in cervical cancer tissues(rp=0.600, p<0.05)9. The expression of OPN in serum level was related to the clinical stage, cytology classification, tumor invasive depth and lymph node metastasis:the serum levels of OPN in Ⅲ～Ⅳ stage patients was higher than that in Ⅰ～Ⅱ stage patients, cytology classification was low-differentiated patients higher than moderately or well-differentiated patients;tumor invasive depth over1/2interstitial patients higher than less than1/2interstitial patients;significantly higher levels were associated with lymph node metastases (p<0.05). There was no significantly difference in different age of the patients (p>0.05)10. The serum level of OPN was overexpression in cervical cancer. Compared with the effective group and the ineffective group of neoadjuvant chemotherapy, the expression of OPN in serum level in effective group was decreased significantly after neoadjuvant chemotherapy(p<0.05). While in the uneffective group, there was no significant difference of the expression OPN in serum level before and after neoadjuvant chemotherapy. Compared with the serum level of OPN before neoadjuvant chemotherapy between effective group and the ineffective group, the effective group was lower than the ineffective grou (p<0.05). Compared with the expression levelof OPN after neoadjuvant chemotherapy between effective group and ineffective group, the effective group was also lower than the ineffective group (P=0.014)11. The expression of OPN in serum level in10cases of cervicalcancer patients was significantly decreased after treatment of concurrent chemoradiotherapy (p<0.05).12. Cervical cancer patients with TCM syndrome differentiations found that the clinical stage of Spleen and kidney Yang syndrome、Liver-kidney Yin deficiency syndrome were significantly later than And card stomachs Hot and humid stasis poison card (p<0.05).There were no statistically significant differences of other different TCM syndrome differentiations (p>0.05).There were no statistically significant differences of OPN mRNA in Cervical cancer tissues in different TCM syndrome differentiations (p>0.05).There were statistically significant differences of HIF-1α mRNA in TCM syndrome differentiations which Liver-kidney Yin deficiency syndrome and Spleen were higher than And card stomach and Hot and humid stasis poison card(p<0.05). There were no statistically significant differences of HIF-1a mRNA in other different TCM syndrome differentiations (p>0.05)Conclusion1. OPNmRNA and HIF-1α mRNA were significantly overexpressed in cervical cancer tissues, and the correlation of them was significantly, which were closely related with clinical pathological features, and played an important role in the occurrence and development of cervical cancer.2. The expression levels of OPN mRNA and HIF-1α mRNA were decreased significantly after neoadjuvant chemotherapy. The expression levels of OPN mRNA and HIF-1α mRNA before neoadjuvant chemotherapy were closely related to the sensitivity and clinical efficacy of chemotherapy,which can be used as important predictors of neoadjuvant chemotherapy in cervical cancer.3. The expression levels of OPN mRNA and HIF-1α mRNA in10cases of cervical cancer patients were significantly decreased after treatment of concurrent chemoradiotherapy.4. Serum level of OPN was significantly overexpressed in cervical cancer, which was closely related with the clinical and pathological features. Serum levels of OPN in cervical cancer patients with neoadjuvant chemotherapy and concurrent chemoradiotherapy were same as cervicalcancertissues’.The level of serum OPN can be as an important predictors of radiotherapy and chemotherapy sensitivity in cervical cancer.5. The expression level of HIF-1a mRNA in the organization of cervical cancer patients was closely related TCM syndrome differentiations:Spleen and kidney Yang syndrome、Liver-kidney Yin deficiency syndrome were significantly higer than And card stomach、Hot and humid stasis poison card.