The Relationship Of Radiosensitivity And DNA Double Strand Breaks Repair Genes In Non-Homologous End Joining Pathway In Cervical Carcinoma

Objective To study on the correlation between the five key genes-DNA1igase IV(LIG4)、X-ray repair cross complementing gene4(XRCC4)、X-ray repaircross complementing gene5(XRCC5)、 X-ray repair cross complementing gene6(XRCC6)、 X-ray repair cross complementing gene7(XRCC7)-expression levelsin Non-homologous End Joining Pathway (NHEJ) and cervical carcinoma and itsradiosensitivity.Methods The mRNA expressions of LIG4、XRCC4、XRCC5、XRCC6、andXRCC7were detected by real-time quantitative reverse transcription-polymerasechain reaction (QRT-PCR) method in61cervical carcinoma tissues and20normalcervical tissues. According to the World Health Orgnization solid tumor responsejudgment standard,the patients of cervical carcinoma were divided into two groupswhich were high radiosensitive and low radiosensitive in order to contrast thedifferentiations of these genes expressions.Meanwhile,with clinical data,methodsanalyzing the relationships between the mRNA expressions of the five genes andclinical stage、 differentiation and pelvic lymph node metastasis of cervicalcarcinoma.Results (1) The mRNA expression of LIG4、 XRCC4、 XRCC5、 XRCC6、andXRCC7in cervical carcinoma tissues compared with normal cervical tissueswere respectively2.88±1.97and5.02±1.87、2.16±0.99and3.72±1.36、2.45±1.52 and3.49±1.41、2.36±1.21and3.23±1.57、2.21±1.85and3.43±2.16,the differenceshave statistical significance(t=4.24、5.47、2.68、2.58、2.47,P=0.000、0.000、0.009、0.012、0.016， respectively).(2) In61cases of cervical carcinoma afterradiotherapy, complete response(CR) were60.7%(37/61), partial response and noChange (PR+NC) were39.3%(24/61).(3) The mRNA expressions of LIG4、XRCC4、XRCC5、XRCC6、and XRCC7between the high radiosensitive group(CR)and the low radiosensitive group(PR+NC) were respectively0.84±0.60and1.30±0.50、1.46±0.58and2.08±0.75、2.07±1.09and2.96±1.07、0.54±0.23and0.72±0.17、0.60±0.34and0.90±0.27.There were statistical significance betweenthe two groups in the five genes expressions(t=2.54、3.24、2.70、2.73、2.97,P=0.014、0.002、0.009、0.008、0.004,respectively).(4) Multivariable partialcorrelation analysis showed that the mRNA expressions of the five genes incervical carcinoma had positive correlation each other except for LIG4andXRCC5.(5)The mRNA expressions of LIG4in the clinical Ⅱ stage group lowerthan Ⅲ stage group in cervical carcinoma patients,the differences had statisticalsignificance (t=-2.75,P=0.008),but other genes had no;The differences of themRNA expressions of the five genes between low-histodifferentiation group andhigh-histodifferentiation cervical carcinoma tissues had not statistical significance(P＞0.05);The mRNA expressions of LIG4and XRCC4of pelvic lymph nodemetastasis patients were above no pelvic lymph node metastasis patients ofcervical carcinoma, the differences had statistical significance(t=3.28、2.61,P=0.002、0.011， respectively),but other genes had no differences.Conclusions (1)The mRNA expression of LIG4、XRCC4、XRCC5、XRCC6and XRCC7in cervical carcinoma tissues was lower than that in normal cervicaltissues, which showed the five genes may play a certain role in the development ofcervical carcinoma.(2) The high gene expressions of LIG4、 XRCC4、 XRCC5、 XRCC6and XRCC7in cervical carcinoma tissues displayed radioresistance,on theopposite,the low expressions of them displayed radiosensitivity, they mightforecast radiosensitivity of cervical and might be molecular targets ofradiotherapy sensitization.(3)The mRNA expressions of the five genes in cervicalcarcinoma had positive correlation each other except for LIG4and XRCC5.(4)Theexpression levels of LIG4mRNA and XRCC4mRNA in cervical carcinoma tissueswere relevant to the progression of cervical carcinoma.