The Expression And Significance Of ATG7 In Early-stage Cervical Squamous Cell Carcinoma

Objectives:Cervical cancer is one of the most common malignant tumors in women,which seriously threaten the women's health and the quality of life.Histopathologically,squamous cell carcinoma is the most common subtype of cervical cancer,accounting for about 75 to 80 percent.It is now thought that the persistent infection of high-risk HPV plays a leading role in oncogenesis of cervical cancer.But,the virus infection alone is hard to clarify the complicated process of development of cervical cancer.Therefore,we still need to explore and comprehend the cellular and molecular mechanisms in the development and progression of cervical cancer,and find the new tumor markers,which are of important significance in prevention,early diagnosis,treatment and efficacy prediction for cervical cancer.In recent years,researches found that autophagy not only maintain the homeostasis in organisms but also is closely related to many physiological and pathological processes.And the relationship between autophagy and tumor had been one of the research hotpots.ATG7 is an E1-like enzyme that is specifically involved in autophagosome formation and is essential for autophagy.This study aim to detect the expression of ATG7 in the early-stage cervical squamous cell carcinoma tissues and the normal cervical tissues,discuss the role of ATG7 in the oncogenesis of early-stage cervical squamous cell carcinoma.Methods:The expression levels of ATG7 were analyzed in 60 samples of early-stage cervical squamous cell carcinoma tissues and 40 samples of normal cervical tissues by immunohistochemistry.Study Group:Selected 60 cases of early-stage cervical squamous cell carcinoma patients with FIGO stage ? A to ? A,who were underwent radical hysterectomy and bilateral pelvic lymphadenectomy in Shandong Province Qianfoshan Hospital from May.2014 to Oct.2017.The age of patients ranged from 31 to 74 years old,with a median of 49 years old and an average of 49.3 years old.8 cases(13.3%)were ? A stage,39 cases(65.0%)were ? B stage and 13 cases(21.7%)in ? A stage.Control Group:Selected 40 cases of patients who were underwent hysterectomy due to leiomyoma or adenomyosis during the same period.The age of patients ranged from 42 to 57 years old,with a median of 49 years old and an average of 49.7 years old.Collect the paraffin specimens mentioned above in pathology department of Shandong Province Qianfoshan Hospital and all the tissues were diagnosed by two pathologists.In addition,we selected 15 cases of the early-stage cervical squamous cell carcinoma tissue samples and 15 cases of normal cervical tissue samples from Mar.2017 to Dec.2017,using the method of RT-PCR to detect the expression of ATG7 in mRNA levels;using the method of Western Blot to measure the expression of ATG7 in protein levels.All data were analyzed by SPSS 22.0 statistics software.Results:1.Immunohistochemistry:The expression of ATG7 mainly located in cell nucleus,with brown or brown granules staining.The positive expression rate of ATG7 in early-stage cervical squamous cell carcinoma tissues and normal cervical tissues was 15.0%(9/60)and 95.0%(38/40),respectively,difference between the two groups has statistical significance(P=0.000).2.RT-PCR:The mRNA of ATG7 was detected in both early-stage cervical squamous cell carcinoma tissues and normal cervical tissues,but the level of ATG7 mRNA in early-stage cervical squamous cell carcinoma tissues was significant lower than in normal cervical tissues,difference between the two group has statistical significance(P<0.0001).3.Western Blot:Compared with normal cervical tissues,the expression of ATG7 in protein levels was significantly decreased in early-stage cervical squamous cell carcinoma tissues.4.No significant correlation was observed between the expression of ATG7 and age,clinical stages,tumor size,pathological type,depth of myometrial invasion and lymph node involvement.Conclusion:1.Compared with normal cervical tissues,the expression of ATG7 was significantly decreased in early-stage cervical squamous cell carcinoma tissues.It indicates that ATG7 may play an important role in the development and progression of early-stage cervical squamous cell carcinoma.2.No significant correlation was observed between the expression of ATG7 and age,clinical stages,tumor size,pathological type,depth of myometrial invasion and lymph node involvement.It indicates that the negative or down-regulated expression of ATG7 may occur in the early stage of cervical squamous cell carcinoma.