The Preliminary Study On Expression Of ATM,?H2AX And CHK2 In Oral Leukoplakia And Squamous Cell Carcinoma

Objective:The aim of this study was to investigate the expression of ATM and its downstream molecules and analyze the correlation between the expression level and clinical parameters in oral leukoplakia(OLK)and oral squamous cell carcinoma(OSCC)patients.The transcription level and translation level of in vitro OLK cells and OSCC cells were also studied.The role of ATM,?H2AX and CHK2 in the initiation and development of OSCC was determined.Moreover,we analyzed a group of OLK patients retrospectively,examined the protein expression of ATM and ?H2AX in samples from the patients,and evaluated their usefulness as biomarkers for predicting the transformation of OLK to oral cancer.Methods: 1.Four OLK tissue and six early OSCC tissues were collected,and different xpression genes were identified by analysis of Affymetrix microarray data on early SCC and a candidate DNA damage repair pathways related gene was analyzed ith literature review.2.In the case-control study,fifteen oral normal mucosa,sixty-one OLK tissue and hirty-three early OSCC tissues,and clinical data of the were patients collected,the xpression of ATM,?H2AX and CHK2 were determined by immunohistochemistry n samples from normal tissues,OLK tissues and OSCC tissues.The clinical ignificance of the proteins were analyzed as well.3.Real-time PCR and Western blotting were performed to confirm the expression of RNA and protein in vitro of ATM and ?H2AX in cell lines.4.In the retrospective study,the correlation of the clinic pathology and the expression f ATM and ?H2AX were analyzed between untransformed cases and malignant- ransformed cases.The clinical value of ATM and ?H2AX was evaluated.Results: 1.DNA damage repair pathways related gene ATM is up-regulated in early OSCC issues and has been selected as a targeted gene based on analysis of microarray ata and literature.2.In vitro results of Real-time PCR demonstrated the ascending trend of mRNA ranscription of ATM and H2 AX in HOK,Leuk1 and HN13.The protein expression f ATM in HN13 was descending and its of ?H2AX was ascending demonstrated y Western blotting.3.Immunohistochemistry demonstrated that positive expression of ATM and ?H2AX ere significantly higher in early OSCC tissues than in OLK and normal tissues.The results revealed a positive relationship between the high expression of the roteins and the risk of oral carcinogenesis.Conclusions: 1.DNA damage repair pathways related gene ATM is one of the up-regulated genes in early OSCC tissues,and it may play a role as a suppressor gene.2.The expression of ATM gene changes at OLK,suggesting DNA damage repair starts in the early stage of OSCC.3.DNA damage repair pathway consisted of ATM and its downstream molecular ?H2AX was involved in oral carcinogenesis,and the high protein expression of ATM and ?H2AX were the risk factors.