Clinical Study On Cervical Cancer Of Expression Of Autophagy Related Protein And DWI

BackgroundCervical cancer morbidity and mortality is the second for the malignant tumor of female in the word. In our country, It is the first in the malignant tumor of female reproductive system. So it has become an important public health problem how to reduce the incidence and mortality of cervical cancer.Cell autophagy is realized for the metabolism of the cell to be updated and organelles, maintain stable biological process. The expression of autophagy related protein and to a variety diseases, especially closely related to the occurrence and development of malignant tumor. Beclin1 is an important protein in cell autophagy, It can be promote the formation of Pre-autophagosome(PAS),mediate other autophagy specificity protein localization in phagophore. p62 is a selective autophagy receptor, autophagy degradation processes is mainly involved in cell transmembrane flow, DNA repaired, mediated ubiquitination protein,also it is reflect the autophagic activity of the labeled protein, mainly involved to participate in the formation of autophagy body. LC-3 is composited by LC-3-Ⅰ and LC-3-II, because LC-3-II content is in direct proportion to the number of the phagophore, therefore LC-3(mainly LC-3-II) can be used as a index of autophagy state. Autophagy related protein expression of beclin-1, LC-3 and p62 protein expression and to investigate the correlation of cervical cancer to further reveal the cervical cancer occurrence and development mechanism, to judge the prognosis of cervical cancer, effective prevention and provide the basis for a new target for therapy for cervical cancer.Currently Diffusion Weighted Imaging(DWI) is the only inspection technology that can be measure the water diffusion in vitro imaging, quantitative evaluation of cervical cancer by DWI image ADC value, can more accurately reflect the invasive carcinoma of cervix tumor functional change, but not can be used for the prediction and assessmentd the prognosis of cervical cancer is the lack of study on the correlation of molecular biology.In this study, Beclin1, p62 and LC-3 were investigated by immunohistochemical method in normal cervical tissue, cervical intraepithelial neoplasia(CIN)and cervical squamous cell carcinoma. Analysis of the relationship between the three proteins and clinical pathology in cervical cancer,As well as the impact on the survival and prognosis of cervical cancer. At the same time ADC values were measured by DWI with different differentiation degree of cervical cancer, investigateed the relationship between ADC values and the molecular biology mechanism of cervical cancer, looked for the early diagnosis of cervical cancer, autophagy targeted therapy and prognosis judgement to provide certain reference basis, also for cervical cancer translational medicine research to provide new idea. ObjectiveTo observe the positive expression of Beclin1, p62 and LC-3 in normal cervix, CIN and cervical cancer, and to analyze the relationship between the expression of these three autophagy related proteins and clinical pathological factors of cervical cancer. Determine the ADC value of high, medium and low differentiated cervical squamous cell carcinoma patients, and study the correlation between the expression of autophagy related protein and ADC value in cervical cancer. Explore the value of diffusion weighted imaging and autophagy related protein expression in cervical cancer. Materials and MethodsImmunohistochemical SP method were used in 191 cases of cervical cancer specimens(cervical squamous cell carcinoma)、63 cases of CIN group specimens and 32 cases of normal cervical tissue specimens.The positive expression of Beclin1, LC-3 and p62 protein markers and semi quantitative scoring method were compared, expression of above-mentioned three kinds protein between the patients with clinical pathological factors were analysised. Also the influence of the total survival time and progression free survival time of cervical cancer were analysised. At the same time, the group of cervical cancer patients with DWI image data after processing the ADC value was compared with the expression of autophagy related protein. Results1. Beclin1 protein was located in cell membrane and the cytoplasm. positive expression in normal cervix group, CIN group and cervical cancer group were respectively 31.3%, 36.5% and 19.4%, with statistical difference(x2=19.323, P =0.000).Beclin1 expression rate in cervical cancer group was significantly lower than normal cervix group and CIN group(P < 0.01, P < 0.001). However the expression rate was no significant correlation with the patient’s age, tumor differentiation, FIGO stage, SCCAg, tumor diameter, muscular infiltration depth and surgery cut edge, death(P > 0.05), but was significant correlation with lymph node metastasis and tumor recurrence(P < 0.05).2. p62 protein was localized in cytoplasm and cell nucleus. positive expression in normal cervix group, CIN group and cervical cancer group rate respectively is 65.6%,65.1%, 73.8%, with statistical difference(x2=9.617, P < 0.01). p62 protein expression rate in cervical cancer group was obviously higher than normal cervix group, CIN group(P < 0.01). However the expression rate was no significant correlation with the patient’s age, tumor differentiation, FIGO stage, tumor diameter, muscular infiltration depth and surgery cut edge, death(P > 0.05), but was significant correlation with SCCAg,lymph node metastasis and tumor recurrence in patients(P < 0.05).3. LC-3 protein was mainly localized in the cytoplasm and nucleus, positive expression in normal cervix group, CIN group and cervical cancer group were respectively 84.4%,73%, 50.3%, with statistical difference(x2=36.291 P=0.000). The score of LC-3 protein in cervical carcinoma group, the positive expression of value was significantly lower than that in normal cervix group and CIN group(P < 0.001, P < 0.01), Besides, The positive expression rate was no significant correlation with the patient’s age, FIGO stage, SCCAg, tumor diameter, surgery cut edge and death(P > 0.05), but was significant correlation with tumor differentiation, lymph node metastasis, muscular infiltration depth and tumor recurrence in patients(P < 0.05).4. The tumor differentiation, lymph node metastases and LC-3 expression was observed risk factors for overall survival time(P < 0.05). Age, FIGO stage, SCCAg, tumor diameter, infiltration depth, cutting edge, expression of Beclin1 and p62. There was no significant correlation with OS time(P > 0.05); SCCAg, lymphatic node metastasis, and expression of Beclin1, p62, LC-3 were observed risk factors influencing the progression free survival time(P < 0.05). Age, Tumor differentiation FIGO stage, tumor diameter, invasion depth and surgery cut edge, there were no significant correlation with PFS(P > 0.05).5. In cervical cancer group, the high differentiation patients was significantly higher than medium differentiation patients, and the average ADC value of the medium differentiation patients was significantly higher than low differentiation patients(P < 0.05).6. In cervical cancer group and highly differentiated in patients with positive expression of LC-3 and ADC value had no significant difference, between medium and low differentiated patients with positive expression of LC-3 and the ADC value has significant difference. Conclusions1. Beclin1 protein expression is lower in cervical squamous cell carcinoma. It has significant difference with lymph node metastasis and recurrence, and it is the risk factor of PFS. So Beclin1 protein may be closely related with the occurrence and development of cervical cancer.2. p62 protein expression is higher in cervical squamous cell carcinoma. It has significant difference with lymph node metastasis, SCCAg and tumor recurrence, and it is the risk factor of PFS. So p62 protein may be closely related with the development and prognosis of cervical cancer.3. LC-3 protein in cervical squamous cell carcinoma shows low expression, and tumor differentiation, lymph node metastasis, muscular layer infiltration depth and recurrence has significant difference and affect overall survival time and risk factors for progression free survival time, LC-3 protein and cervical cancer occurrence, development and prognosis are closely related.4. The ADC values could not only diagnose for the differentiation degree of cervical squamous cell carcinoma, but also could be used to the prognosis of cervical cancer combined with LC-3.