Expressions And Significance Of ARHI And BECN1 In Breast Cancer

Background:Breast cancer is a common clinical malignancy which threaten the health of women all over the world.Its incidence rate has been on the rise and this disease has tended to affect younger women in recent years.Oncogene and tumor suppressor genes are both exist in the normal cells of the body.Under normal circumstances,they are in a "balanced state" with ositive and negative signal which regulate proliferation and differentiation.When the internal or/and external factors make the inactivation of tumor suppressor gene or activation of oncogene,this kind of "balance" will be broken,that can result in the transformation of normal cells into cancer cells.The occurrence and development of breast cancer is a accumulated process of genetic mutation,the inactivation of tumor suppressor genes play an important role in the evolution of breast cancer.ARHI(Aplasia Ras homolog member?),also known as NOEY2 or DIRAS3,is the first reported tumor suppressor gene of the small G protein Ras superfamily,it is related to tumor and autophagy.BECN1,which is a homologue of Atg6 in yeast,can start autophagy after binding to PI3 K and Vps34,it is inextricably linked to tumor and autophagy such as ARHI.Studies have found that ARHI and BECN1 are down-regulated or missing in breast cancer,ovarian cancer,pancreatic cancer and other tumors as two important tumor suppressor genes.However,there is not much research on the correlation between ARHI and BECN1.Objective:The purpose of this study is to analyze the relationship between ARHI and BECN1 with the clinical and pathological parameters of breast cancer by investigating their expression levels in the breast benign lesions,breast cancer and adjacent tissues,and to explore the clinical significance of ARHI and BECN1 in breast cancer.The other purpose of this study is to explore a theoretical basis for screening of highly aggressive breast cancer and guiding clinical therapy by analyzing the difference of the expression levels between different molecular subtypes of breast cancer.Method:We collected 123 cases patients' wax block organizations who receivied surgery in the Second Affiliated Hospital of Dalian Medical University and the Central Hospital of Dalian from January 2015 to December 2016,including 24 benign breast lesions,84 breast cancer and 15 paracancerous tissue.The expression levels of ARHI and BECN1 in benign lesions,breast cancer and adjacent tissues were detected by the method of immunohistochemistry(SP).The relationship between the two indicators and their association with the clinicopathologic parameters in breast cancer were analyzed by statistical methods.Results: 1? The positive rates of ARHI in benign breast lesions,breast cancer and paracancerous tissue were 87.5%(21/24),46.4%(39/84)and 93.3%(14/15)respectively,and the positive rate in breast cancer is significantly lower than the other two groups,with statistical significace(P<0.01).The expression of ARHI in breast cancer was correlated with the degree of pathological differentiation,lymph node metastasis and the expression of PR(progesterone receptor)(P<0.05),but there was no significant correlation with the age,menstrual status,family history of cancer,clinical stages,the size of tumor,vascular cancer embolus or nerve invasion,ER,Her-2 and CK5/6(P>0.05).2? The positive rates of BECN1 in benign breast lesions,breast cancer and paracancerous tissue were 91.7%(22/24),51.2%(43/84)and 86.7%(13/15)respectively,and the positive rate in breast cancer is significantly lower than that in the other two groups,with statistical significace(P<0.05).The expression of BECN1 in breast cancer was correlated with clinical stages,the degree of pathological differentiation,lymph node metastasis,the degree of pathological differentiation,lymph node metastasis and the expression of Her-2,but there was no significant correlation with the age of onset,menstrual status,family history of cancer,the size of tumor,nerve invasion,ER,PR and CK5/6(P>0.05).3? In 84 cases of breast cancer tissues,the expression of ARHI was positively correlated with the expression of BECN1(r=0.288,P=0.008).4? The positive rates of ARHI and BECN1 in Luminal A and Her-2 enriched breast cancer were high and close,followed by Luminal B type,the lowest positive rate is in triple negative breast cancer.In every molecular subtype,there was a statistical difference in the expression of ARHI(x2=22.040,P=0.000),while there was no statistical difference in the expression of BECN1(x2=6.330,P=0.097).Conclusion: 1? The positive expression rates of ARHI and BECN1 in breast cancer were both lower than that in paracancerous tissue and benign breast lesions.2? The positive expression rates of ARHI and BECN1 in Luminal A and Her-2 enriched breast cancer were high and close,and the expression rate of ARHI was the lowest in triple negative breast cancer.The expression of ARHI in every molecular subtype of breast cancer had a statistical difference.3? The expressions of ARHI and BECN1 in breast cancer were positively correlated.4? In breast cancer,the combined detection of ARHI and BECN1 can help us assess the degree of malignancy,determine the prognosis and guide clinical therapy,etc.