A Study On The Expression Of BRD4 In Cervical Cancer And Its Correlation With Clinical Data

Objective:The purpose of this study is to explore whether there is a difference in the expression of BRD4 between cervical cancer and normal cervical tissues,and whether the expression of BRD4 is related to the FIGO stage and clinicopathological data of cervical cancer,so as to provide clinical basis and treatment direction for targeted therapy of cervical cancer.Methods :1.The histological specimens of 51 cases of cervical cancer confirmed by pathologists who underwent radical hysterectomy in the second Hospital of Jilin University from December 2020 to December 2021 were collected.51 normal cervical tissue samples confirmed by pathologists to perform total hysterectomy for uterine benign lesions in the second Hospital of Jilin University in the same period were collected.All specimens were fixed by 4% paraformaldehyde and made into paraffin sections.2.The expression of BRD4 protein in normal cervical tissue and cervical cancer tissue was detected by immunohistochemical staining.Judging criteria: when the nucleus staining is yellow or brown（brown when the color is dark）,the expression of BRD4 is positive;if only staining the cytoplasm,the nucleus is not stained or the nucleus and cytoplasm are not stained,the expression of BRD4 is negative.The image was collected by ordinary optical microscope and pathological image acquisition system,and the immunohistochemical image data were analyzed by image analysis software Image Pro Plus6.0（IPP）.IPP software will automatically calculate the optical density value（Integrated Optical Density,IOD）of the positive area,and calculate the area of the area at the same time.Finally,we take the average optical density value（Mean Optical Density）,that is,the ratio of integral optical density value to area under the visual field（IOD/Area）.Finally,the average value and standard deviation of each photo of the same experimental group were calculated.When measuring the average IOD,three or more measurements of different visual fields were carried out with all the films,and the average was taken in order to reduce the experimental error.The average IOD calculated by IPP reflects the expression of BRD4 in cervical cancer and normal cervical tissues.3.Statistical methods were used to analyze the indexes.Nonparametric rank sum test Mann-Whitney U test（Mann-Whitney Utest）was used to test the difference of BRD4 expression between cervical cancer patients and normal cervical tissues.LSD-t test was used to analyze the correlation between the expression of BRD4 and the FIGO stage and the depth of interstitial invasion of cervical cancer.Independent sample t-test was used to analyze the correlation between the expression of BRD4 and the degree of differentiation,lymphatic vascular space invasion,lymph node metastasis,family history and smoking history of cervical cancer.Mann-Whitney U test analyzed the correlation between BRD4 expression and vaginal stump and para-uterine tissue infiltration.The correlation between BRD4 expression and age,SCC,16 / 18 HPV-DNA load and reproductive history was tested by Spearman（Spelman）correlation analysis,and the correlation between Ki67 positive rate and BRD4 expression was analyzed by Pearson（Pearson）correlation coefficient test.P < 0.05 is considered to be statistically significant.Results:1.Compared with normal cervical tissues,the expression of BRD4 in cervical cancer tissues was significantly higher（p < 0.001）.2.BRD4 expression was not correlated with FIGO stage（stage I,II,III）,pelvic lymph node metastasis（p = 0.642）,vaginal stump and para-uterine invasion（p = 0.162）,lymphatic vascular space invasion（p = 0.485）and cervical invasion depth（p = 0.703）.3.BRD4 expression was not correlated with age,smoking history,family history,reproductive history,SCC,HPV-DNA load and Ki67 positive rate in patients with cervical cancer.Conclusion:1.Compared with normal cervical tissues,the expression of BRD4 in cervical cancer tissues was significantly higher.2.There was no correlation between BRD4 expression and FIGO stage（stage I,II,III）,pelvic lymph node metastasis,vaginal stump and para-uterine invasion,cervical interstitial depth and lymphatic vascular space invasion,but few cases were included in the study,and further study is needed to expand the sample size.3.There was no correlation between BRD4 expression and HPV-DNA load and Ki67 positive rate,but few cases were included in the study,so it is necessary to expand the sample size for further study.4.There was no correlation between BRD4 expression and cervical cancer age,smoking history,family history,SCC,reproductive history.5.BRD4 is expected to be a target for targeted therapy of cervical cancer.