The Expression And Clinical Significance Of XRCC4in Breast Cancer

BackgroundBreast cancer is the most prevalent cancer in women around the world, becoming the fastest growing cancer in urban mortality. DNA double strand breaks(DSBs), which happen at relative or neighboring bases in both strand, is the crucial point among those pathogenesis of breast cancer. As one of the most severe injuries of cells, DSBs can cause deletion and rearrangement of genetic information and subsequently result in apoptosis or mutation. DSBs repair involves two signaling pathway:non-homologous end joining(NHEJ) and homologous recombinational (HR). NHEJ, which is the mainly repair mode in eukaryotes,means with the help of repairable component, DNA at the ends of the fractures connect directly independent of the DNA homology. What’s more, X-ray repair cross complementing protein4(XRCC4) playing an important role in NHEJ pathway, is the vital housekeeping gene about maintaining the stability of genome. Previous studies have con^med that single nucleotide polymorphism (SNP) in XRCC4is relevant to the risk of breast cancer, however, less researches have been done about protein expression in breast cancer tissues.ObjectiveDepended on various clinical data collection and tissue microarray, through studying on XRCC4expression in respectively breast cancer tissues and adjacent normal tissues, and subsequently combine the results with clinicopathological parameters and overall survival (OS), this research is aimed at investigating whether XRCC4can be treated as breast predictor and prognostic factor, and further analysising the expression of XRCC4in different subtypes of breast cancer, and guiding clinical therapy.MethodsCollect284surgical specimens from breast cancer patients and77specimens about adjacent normal tissue in them; then collect132surgical specimens from triple negative breast cancer patients and90specimens about adjacent normal tissue in them, after making them into tissue microarray, we can investigate the expression and clinical significance of XRCC4in respectively breast cancer tissues, triple negative breast cancer tissues and adjacent normal tissues by using immunohistochemical method (Envision method). SPSS19.0software applications of the data will be used for statistical analysis. P<0.05believe that the results were statistically significant. McNemar test is used for the comparison of paired two sample rate between cancer tissues and adjacent tissues. Pearson chi-square test is used for researching the relationship of protein expression and clinicopathological parameters in cancer tissues. Logistic regression is used for analysising of factors that affect XRCC4protein expression. Kaplan-Meier method is used for estimating survival of different groups and doing Log-rank test. At last, COX model is used for overall survival multivariate analyze and the role it played in triple negative breast cancer prognosis.Result1、In the breast cancer, the cancer tissue XRCC4expression levels significantly lower than the adjacent tissues (27.8%VS54.5%, P<0.01); The triple-negative breast cancer get the same result (25.8%VS77.8%, P<0.01)2、In breast cancer, XRCC4expression levels have significant differences in different histological grade(P=0.04)、lymph node metastasis status(P=0.045)、tumor size (0.036) and TNM stage (P=0.04); compared with different histological grade (P=0.047), lymph node metastasis status (P=0.027), and KI67(P=0.016) in triple negative breast cancer.3、In breast cancer with different molecular types, XRCC4expression levels have not significant differences in different types.4、In triple negative breast cancer, XRCC4-positive group has longer overall survival period than negative group, but the difference was not statistically significant (P=0.170>0.05); Cox proportional hazards regression model suggest that pathological types are independent prognostic factors for triple negative breast cancer rather than XRCC4expression levels.ConclusionsXRCC4expression in breast tissues is in line with the general characteristics of the tumor suppressor gene, suggesting that might be involved in the development and progress of breast cancer. And its expression absence is closely related to the breast cancer malignant behavior. As an important component in the NHEJ pathway, XRCC4affect breast cancer evolution mechanism worth further study.