The Expression And Clinical Significance Of MiR-145、miR-34a And Bcl-2 Protein In Different Degrees Cervical Lesions

Objective: To explore the expressions of miR-145, miR-34 a and Bcl-2 protein in different degrees cervical lesions tissues of Uyghur and Han women in Xinjiang and their association with clinicopathological characteristics of cervical carcinoma. Methods:Fifty-eight specimens of cervical carcinoma, sixty specimens of cervical intraepithelial neoplasia Ⅱ~Ⅲ level(CINⅡ~Ⅲ level) and thirty-two specimens of non-tumor tissue of Uyghur and Han women patients were collected. Quantitative Real-time PCR was used to detect the expressions of miR-145 and miR-34 a in different degrees cervical lesions tissues. The correlations between the expressions levels of miR-145 and miR-34 a in cervical lesions of different degrees of Uyghur and Han women and related clinicopathological characteristics of cervical carcinoma were further analyzed. Receiver operating characteristic curve(ROC curve) analyses the ability of potential biomarkers to determine cervical carcinoma. The expressions of Bcl-2 in the all of different degrees cervical lesions tissues were detected by immunohistochemistry. The relationship between the Bcl-2expression and the clinicopathological characteristics of cervical carcinoma was analyzed.Results: The expressions of miR-145 and miR-34 a in cervical carcinoma tissues were statistically significantly lower than those in CINⅡ~Ⅲ level tissues and non-tumor tissues(P<0.05) but no obviously different was found between women with Uyghur and Han ethnicities(P>0.05). The expression of miR-145 was associated with the differentiation degrees and FIGO stage and lymph node metastasis(P<0.05), the expression of miR-34 a was associated with the tumor size and FIGO stage and lymph node metastasis(P<0.05),no significant associations were found between the level of miR-145 and miR-34 a and other clinicopathological characteristics of cervical carcinoma, such as age, pathologicaltypes, myometrial invasiond and parametrial infiltration(P>0.05). The expressions of miR-145 and miR-34 a were positively associated in cervical carcinoma tissues and CINⅡ~Ⅲ level tissues(r=0.312, P=0.017; r=0.444, P=0.000). Receiver operating characteristic curve(ROC curve) analysis show that miR-145 yielded a receiver-operator characteristic curve area(AUC) of 0.786(sensitivity 91.7% and specificity 65.2%) to discriminating cervical carcinoma differentiation degrees; miR-34 a yielded AUC of 0.748(sensitivity70.3% and specificity 76.2%) to discriminating cervical carcinoma tumor size; miR-145 and miR-34 a yielded AUC of 0.779(sensitivity 77.8% and specificity 61.5%) and 0.756(sensitivity 73.3% and specificity 69.2%) to discriminating lymph node metastasis.miR-145 and miR-34 a yielded AUC of 0.814(sensitivity 78.1% and specificity 62.1%)and 0.889(sensitivity 87.5% and specificity 81.0%) to discriminating cervical carcinoma patients from normal subjects. MiR-34 a yielded AUC of 0.767(sensitivity 78.3% and specificity 70.7%) to discriminating patients with cervical carcinoma from CINⅡ~Ⅲlevel patients and 0.810(sensitivity 83.7% and specificity 70.7%) to determining cervical carcinoma from all cases. The positive rate of Bcl-2 protein in normal cervical tissue,CINⅡ~Ⅲ level tissue and cervical carcinoma tissue respectively was 6.25%, 60% and77.59%. There was significant difference in the positive rate of Bcl-2 in the three kinds of tissues(P<0.05). The expression of Bcl-2 protein was associated with the differentiation degrees and FIGO stage(P<0.05). No significant correlation between the age,pathological types and lymph node metastasis(P>0.05). The level of expressions of miR-145 and miR-34 a were negatively correlated with the level of Bcl-2 protein in cervical carcinoma tissues and CIN Ⅱ ~ Ⅲ level tissues(P<0.05). Conclusion: The expressions of miR-145 and miR-34 a were no significant differences between the different ethnic groups. Down-regulation of miR-145, miR-34 a and up-regulation Bcl-2 may be involved in the oncogenesis and development of cervical carcinoma, which may become to be a novel and potential biomarkers for early diagnosis, prognosis and targeted therapy of cervical carcinoma.