| ObjectiveThis study is to detect microRNA-96(miR-96) expressions in cervical cancer tissues and their associations with the clinical pathologic characteristics. To investigate the expressions of miR-96pre-and post-neoadjuvant chemotherapy and to explore the influence of the treatment on miR-96expressions and its relationships with chemotherapy response, chemo-sensitivity and clinicopathological features, then evaluate the possibility of miR-96as a prognosticator of chemo-sensitivity and chemo-response in cervical squamous cell carcinoma. And analysis miR-96expressions in carcinoma tissues and the connection with Traditional Chinese Medicine, and to evaluate the value and prospect of the method of integrative medicine in treating cervical cancer.MethodsThe expressions of miR-96in52cases of cervical cancer tissues and28cases of normal cervical tissues were detected by stem-loop real time PCR which is also used to investigate the expressions of miR-96in28cases of cervical squamous cell carcinoma (Ib2～IIa) before and after neoadjuvant chemotherapy-The relationships of miR-96expressions and related clinicopathologic characteristics were further analyzed, and to explore effects of the chemotherapy on the change of miR-96and its relationships among clinical efficacy, chemosensitivity and clinical pathologic characteristics. In this paper, TCM syndrome differentiation was used to analysis the expression levels of miR-96in cervical cancer to explore the relationship between miR-96and TCM.Results 1. MiR-96expressions in the52cases of cervical tumor tissues45.59(15.19,139.61) were much higher than the28cases of normal cervical tissues0.94(0.78,1.11), the differences of statistic were remarkable (p<0.05).2. The expressions of miR-96in cervical cancer tissues were closely related to the clinicopathologic features. Compared to the expressions in G1tumors16.78(6.13,66.67), miR-96expressions significantly increased in G2and G3tumors61.61(17.74,183.42)(p<0.05). Compared with the squamous cell cancer27.28(13.35,91.00), cervical adenocarcinoma showed a much higher level of miR-96155.67(57.77,270.61)(p<0.05). miR-96expressions at I stage, II stage and III-IV stage were15.41(7.52,26.26),85.15(68.32,194.76) and462.08(422.57,1028.65)respectively; expressions of III-IV stage were much higher than I stage and II stage (p<0.05) II stage showed a higher level of miR-96than that in I stage (p<0.05). With lymph node metastasis163.46(28.95,205.62) was significantly lower than those without lymph node metastasis14.16(6.99,22.61)(p<0.05). Tumor invasive depth<1/2interstitial patients13.79(5.14,25.649) showed a lower level of miR-96than that in≥1/2interstitial patients24.72(14.44,141.79),(p<0.05). The expression of miR-96was not correlated to the age(p>0.05).3. The relative quantitative results of miR-96(2-ΔΔCT) before treatment was3.40(2.01,6.86) times higher than the tissues after the treatment, the statistical difference was significant(p<0.05).4. The relative quantitative result of the changes of miR-96in cervical carcinoma patients between pre-chemotherapy and post-chemotherapy, was closely related with clinicopathological features:Cytology classification was low-differentiated or moderately patients2.51(1.21,3.26) lower than well-differentiated patients8.22(5.21,15.39)(p<0.05); tumor invasive depth <1/2interstitial patients5.66(4.06,14.09) higher than≥1/2interstitial patients1.91(0.90,2.96)(p<0.05); with lymph node metastasis1.79(0.86,2.64) was significantly lower than those without lymph node metastasis5.43(4.04,12.84)(p<0.05). There was no significantly difference with patient age and clinical stage(Ib2-IIa)(p>0.05).5. Compared to the invalid group of Neoadjuvant Chemotherapy, miR-96expressions in valid group were declined obviously after the treatment (p<0.05), While there was no much changes of miR-96expressions in the invalid group (p>0.05).Before neoadjuvant chemotherapy the effective group showed a lower miR-96expressions than the ineffective group (p<0.05), After neoadjuvant chemotherapy the effective group also showed a lower miR-96expressions than the ineffective group (p<0.05)6. MiR-96expressions in carcinoma tissues before the chemotherapy were intimately associated with the three Dultrasound parameters FI, VI, VFI and residual tumor volume percentage(p<0.05). There were no obvious links with the tumor tissue size before chemotherapy (p>0.05).7.According to TCM syndrome differentiations:compared to the Liver qi depression card and Hot-humid stasis poison card, miR-96expressions in the clinical stage of Liver-kidney Yin deficiency card and Spleen-kidney Yang deficiency card were much higher (p<0.05). But there were no obvious differences of miR-96expressions in Liver-kidney Yin deficiency syndrome and Spleen-kidney Yang syndrome or in Liver qi depression card and Hot-humid stasis poison card (p>0.05).Conclusion1.The aberrant expressions of miR-96and its intimate association with clinicopathological features suggest it might play a role as an oncogene in the tumorigenesis and progress of cervical cancer, and is closely linked with the evolution and poor prognosis of cervical cancer.2. Neoadjuvant chemotherapy can obviously reduce miR-96expressions in the tumor tissues, suggested that it was closely related to the chemosensitivity and chemotherapy response, which means miR-96could serve as a predictor in the response and sensitivity of chemotherapy in cervical carcinoma.3. MiR-96expressions in cervical cancer tissues were closely related with TCM syndrome differentiations:Spleen-kidney Yang deficiency syndrome, Liver-kidney Yin deficiency syndrome showed a higher levels than Liver qi depression card and Hot-humid stasis poison card. |
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