The Impact Of Laptm4b And P27^Kip1Expression On The Clinical Significance In Breast Cancer

Background:Breast cancer is a common and frequently-occurred malignant tumor in female,and severely threats female health.Therefore,finding key gene mutations as medication therapeutic target and molecular markers for clinical treatment plays a vital role for early diagnosis and effective treatment of breast cancer.Lysosome-associated protein transmembrane 4B（LAPTM4B）is a new gene initially isolated from hepatocellular carcinoma in 2000,and shows high expression in most hepatoma carcinoma cells and low or no expression in normal hepatic tissue.As LAPTM4 B facilitates development and progression of liver cancer and is related with poor prognosis of liver cancer,it is expected to become an important target for diagnosis and treatment of liver cancer.In lung cancer,LAPTM4 B inhibits degradation of EGFR by binding PI-4,5-diphosphonic acid（PIP2）,while in some malignant tumors,it enhances cancer by activating AKT.However,the mechanism of action in breast cancer and its relation with clinical characteristics of breast cancer remain unclear.Being a cyclin-dependent kinase inhibitor（CKI）,p27^Kip1,as a cancer suppressor gene,plays a vital role in facilitating apoptosis of cancer and regulation of cell cycle.The p27^Kip1 inhibits development and progression of various malignant cells,and it has been suggested that low expression of p27^Kip1 is related with poor prognosis.Therefore,p27^Kip1 is expected to become a new prognostic indicator and a new target spot of genetherapy.It has been demonstrated that,in liver cancer and gallbladder carcinoma,overexpression of LAPTM4 B inhibits expression of p27^Kip1,while silenced LAPTM4 B results in improved expression of p27^Kip1.There is no relevant research concerning the correlation and clinical significance in breast cancer.Therefore,it is highly necessary to discuss the expression of LAPTM4 B and p27^Kip1 in breast cancer and their correlation is highly necessary to guide the diagnosis and treatment of breast cancer and judgment of prognosis.Objective:（1）Find out expressions of LAPTM4 B and p27^Kip1 in breast cancer tissue.（2）Discuss whether the two are correlated in breast cancer;（3）Discuss the clinical significance of the two for diagnosis and treatment of breast cancer.Methods: A total of 145 filed breast pathological paraffin blocks,which were excised in the second affiliated hospital of Dalian medical university from December2013 to December 2016 were collected,including 100 cases of breast cancer,20 cases of benign fibroadenoma,and 25 cases of para-cancer normal tissue.SP immunohistochemical method was used to test expressions of LAPTM4 B and p27^Kip1 in breast cancer,fibroadenoma and normal tissue.SPSS statistical software was adopted to analyze the correlation between LAPTM4 B 和 p27^Kip1 as well as their respective relations with clinical features of breast cancer.Results:（1）The positive expression rates of LAPTM4 B protein are 74.0%（74/100）in the breast cancer tissues,40.0%（8/20）in the benign fibroadenoma tissues and 28.0%（7/25）in the para-cancer normal tissues,while the positive expression rates of p27^Kip1 are 31.0%（31/100）,65.0%（13/20）and 76.0%（19/25）respectively in the breast cancer tissues,the benign fibroadenoma tissues and the para-cancer normal tissues.（2）In breast cancer,expression of LAPTM4 B is related with lymph node（P=0.019）and TNM staging（P=0.001）,and shows no relation with patient age,tumor size,vessel invasion,ER,PR and HER2 expression（P>0.05）;Expression of p27^Kip1 is related withtumor size（P=0.025）and lymph node（P=0.001）,while it shows no relation other factors（P>0.05）.（3）Expressions of LAPTM4 B and p27^Kip1 in breast cancer show significant negative correlation（P=0.003,r=-0.293）.Conclusions:（1）LAPTM4B protein shows significantly higher expression in most breast cancer tissues than in benign fibroadenoma tissue and para-cancer normal tissue.On the contrary,the expression of p27^Kip1 is significantly higher in normal breast tissue than breast cancer tissue.（2）In breast cancer,LAPTM4 B is positively correlated with lymph node status and TNM staging,while p27^Kip1 is negatively correlated with tumor size and lymph node status.（3）In breast cancer,the negative correlation of LAPTM4 B and p27^Kip1 is significant.The two might be involved in the development and progression of breast cancer and might be therapeutic target spots of breast cancer.