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Expression Of BECN1,LC3 And MTOR And Their Clinical Significance In Cervical Lesions

Posted on:2018-03-10Degree:MasterType:Thesis
Country:ChinaCandidate:J ZhangFull Text:PDF
GTID:2334330518487625Subject:Obstetrics and gynecology
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China’s annual new cases of cervical cancer was more than 100 thousand,and showed the trend of younger significantly.Surgery and radiotherapy are the effective methods for the treatment of cervical squamous cell carcinoma,but the physiological and organ damage caused by these cannot be reversed,so seeking a therapy which has less destructive and side effects is extremely urgent.Targeted therapy,at the cellular and molecular level,has been directed against specific cancer sites that specifically kill target cells without affecting normal tissues.Therefore,the pursuit of accurate and effective is the future direction of treatment of cervical cancer.Autophagy,as a physiological function of cells,and the form of death caused by over activation which similar to apoptosis,appears to offer a new dawn for cancer treatment.Therefore,autophagy related genes may be the potential targets for the treatment of malignant tumors.In these genes,as a promoter of autophagy,BECN1 positively regulates autophagy.MTOR,as the most critical regulator,inhibits autophagy and LC3 B is a marker of autophagic modular structure,which reflects the activity of autophagy.According to the 2014 fourth edition of the WHO classification of female genital system tumors.In this study,LSIL,HSIL,cervical squamous cell carcinoma were taken as the research object.Using immunohistochemical Super Vision method and FISH technology to longitudinal detect the mRNA and protein expression level of the autophagic gene in cervical lesions.The different expression of BECN1,LC3 B and mTOR on the horizontal in step by step in cervical lesions.Tocomprehensively evaluate the relationship between autophagy activity and cervical lesions.The results showed that the protein expression of BECN1 in LSIL,HSIL and cervical squamous cell carcinoma was 21.46±19.48,12.93±11.67,6.28±5.89,while in normal cervical tissues,the expression was36.66±23.28.With the progress of cervical lesions,the expression of BECN1 was down regulated,and lower than that in normal cervical tissues.The difference between the groups was statistically significant(P<0.05).The expression of mRNA also showed the same trend.The protein expression of LC3 B in LSIL,HSIL and cervical squamous cell carcinoma was 22.63±15.09,12.61±8.96,6.99±5.71 and the expression in normal cervix was about 34.84±15.91.The results showed that the expression of LC3 B in cervical lesions was lower than that in normal cervix,and with the development of cervical lesions,the expression level was lower,the difference between the groups was statistically significant(P<0.05).The mRNA expression of LC3 B also showed similar trend.The expression of mTOR in HSIL and protein in the cancer group was 24.02±17.48,35.48±19.65,was significantly higher than that in normal cervical group(6.90±6.69),and the expression of LSIL protein(12.02±9.48)compared with the normal cervix showed no significant difference(P>0.05).With the development of cervical lesions,the expression level of mTOR was higher,and same trend was similar with mRNA.The expression of BECN1 was correlated with the clinical stage and lymphatic metastasis,namely,low expression in patients with lymph node metastasis,the higher the clinical stage,the less expression.LC3 B was correlated with the degree of tumor differentiation,and was low in the patients with low differentiation.However,mTOR was related to lymphatic metastasis and showed high expression in the patients withlymph node metastasis.Meanwhile in cervical squamous cell carcinoma:The expression of BECN1 was positively correlated with LC3B(r=0.642,P < 0.01),meanwhile negatively correlated with mTOR expression(r=-0.418,P<0.01).But there was no correlation between BECN1 and mTOR expression.To sum up,according to the expression of BECN1,LC3 B and mTOR in cervical lesions and normal cervix,reflect the autophagic activity decreased with the progression of the lesion,and showed obvious autophagy defects in HSIL and cervical carcinoma group.This may suggest that low levels of autophagy may be one of the factors contributing to the progression of cervical lesions.At the same time,the protein expression results of BECN1,LC3 B and mTOR were consistent with the results of mRNA expression,suggesting that the interaction and interference between the key genes in the transcription and translation period.In addition,the expression of autophagy related genes was associated with lymph node metastasis,tumor cell differentiation and clinical stage.It is speculated that autophagy may influence the prognosis of patients with cervical cancer.
Keywords/Search Tags:Autophagy, cervical lesions, targeted therapy, BECN1, LC3B, mTOR
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