Expression Of PTPN1 And PTPN12 In Triple-negative Breast Cancer And Its Relationship With Prognosis

Breast cancer is the first major malignant tumor that threatens women's health.According to the China Cancer Registration Annual Report 2015,six people are diagnosed with malignant tumors in China every minute,five people die of cancer,including female breast Cancer incidence of the most,the incidence rate of 42.55/10 million people,accounting for the incidence of all malignancies in 17.10%,only 2015 China's new breast cancer patients up to27.2 million people.Triple negative breast cancer(TNBC)refers to the expression of epidermal growth factor receptor-2(HER2/neu),estrogen receptor(ER),estrogen receptor(ER)Progesterone receptor(PR)were not expressed in a tumor subtype.TNBC accounts for 10% to 20% of all breast cancer,mostly among young patients,and is more common among African-American women[1].TNBC tumors are usually larger,higher in classification,often in the diagnosis of lymph node metastasis,and biologically more invasive [2].Although TNBC patients have a higher clinical response rate for preoperative(neoadjuvant)chemotherapy,they have a higher prognosis than other breast cancer subtypes [3].Despite the primary treatment of adjuvant chemotherapy,the 5-year survival rate of metastatic TNBC patients is still less than 30% [3].PTPN1 is also known as the Protein Tyrosine Phosphatase 1B(PTP1B),a family of protein tyrosine phosphatases(PTP),which coats with protein tyrosine kinases(PTK)Phosphorylation of phosphorylation,a signal transduction pathway involved in a large number of growth factors plays an important role in regulating cell growth,differentiation,metabolism,gene transcription and immune response [4].PTPN1 gene is located in 20q13,this region is associated with the poor prognosis of breast cancer,so further analysis of PTPN1 in breast cancer etiology of the functional role is essential.Julien et al [5,6] found that the lack of PTPN1 can delay the development and progression of breast cancer,specific PTPN1 inhibitors in the prevention of lung metastasis plays an important role.PTPN1 down-regulates Ras-MAPK and P13K-Akt pathway,down-regulates Erb B2/ErbB3 activity,and regulates the stability of CyclinD1 and p27 proteins through its substrate tyrosine residue phosphorylated protein p62 Dok.Therefore,in triple-negative breast cancer,PTPN1 may be a new target for the treatment of human breast cancer.Protein tyrosine phosphatase PTPN12(also known as PTP-PEST)is one of the important members of the tyrosine phosphatase family.PTPN12 dephosphorylates HER1/EGFR and HER2 in breast cancer cells [7,8].PTPN12 can inhibit cell migration by dephosphorylation of cytoskeletal related proteins,such as puerarin or Pyk2 [9],and by regulating Src function.In another study,mutations in PTPN12 were found in TNBC,but were not found in other breast cancer subtypes.In addition,PTPN12 showed tumor inhibitory activity in cultured human mammary epithelial cells and metastatic mouse models associated with dephosphorylation of HERl/EGFR,HER2 and PDGFR-[7].Objective:To investigate the expression of PTPN1,PTPN12,EGFR and CK5 / 6 proteins in TNBC tissues,and to analyze the relationship between the expression of PTPN1 and PTPN12 protein and the clinicopathological features and prognosis.The results provide a preliminary experiment for the prognosis of TNBC and the selection of therapeutic target Theoretical evidence.Methods:Screening of the Fourth Hospital of Hebei Medical University,Department of Pathology in January 2002 to December 2011 during the clinical and pathological data of the three cases of triple negative breast cancer specimens for the study of all patients with radical surgery,all patients are female,and There were no radiotherapy / chemotherapy and endocrine therapy before operation,and 80 cases of paracancerous breast tissue with more than5 cm cancer tissue were used as control group.According to the fourth edition of "WHO Breast Cancer Classification" in 2012,the clinical stage of TNM staging of AJCC seventh edition was performed by two experiencedpathologists.The immunohistochemical SP method was used to detect the tumor The expression of PTPN1,PTPN12,EGFR and CK5/6 in the tissues was discussed,and the relationship between the expression of PTPN1,PTPN12,EGFR and CK5/6 was discussed.Results:1 Patients in general: 208 cases of triple-negative breast cancer in the age of ? 50 years old in 95 cases,> 50 years of age in 113 cases;breast invasive ductal carcinoma in 161 cases(77.4%),breast medullary carcinoma in 22cases(10.6%),25 cases(12.0%)of other types of breast cancer,including 28 cases of death,20 cases(71.4%)of breast invasive ductal carcinoma,2 cases(7.1%)of medullary carcinoma of the breast,6 cases of special type of cancer21.4%).There were 103 patients with T1 stage,99 cases of T2 stage,6 cases of T3 stage and 0 cases of T4 stage.49 patients with clinical stage ?,137 cases in stage ?,22 cases in stage ? and 0 cases in stage ?.No lymph node metastasis in 132 cases,there are 76 cases of lymph node metastasis.2 The positive expression rates of PTPN1 protein were 37.5%(78/208)and 31.3%(25/80)respectively in the three-negative breast cancer tissues and corresponding adjacent breast tissues,respectively.The positive expression rate of PTPN1 protein in triple negative breast cancer tissues was There was no significant difference between adjacent tissues(P> 0.05).The expression of PTPN1 in 208 cases of triple negative breast cancer was 37.5%(78/208),the lowest was 62.5%(130/208).The expression of PTPN1 was correlated with T stage(?~2 = 9.635,P = 0.007),lymph node metastasis(?~2 = 16.255,P = 0.000)and clinical stage(?~2 = 24.303,P = 0.000),the difference was statistically significant(P <0.05),but not with the age(?~2 = 0.069,P = 0.792)and pathological type(?~2 = 0.377,P = 0.539),the difference was not statistically significant(P> 0.05).3 The positive expression rate of PTPN12 protein in 208 cases of triple negative breast cancer was lower than that in control group,the positive expression rates of PTPN12 protein in triple negative breast cancer tissues and corresponding adjacent breast tissues were 57.7%(120/208)and 92.5%(74 /80),the difference was statistically significant(P <0.05).In the 208 cases of triple-negative breast cancer,the expression of PTPN12 was 42.0%(87/208),26.0%(54/208)was weakly positive,28.0%(58/208)Positive,4%(8/208)patients were strongly positive.The expression rate of PTPN12 in 208 cases of triple negative breast cancer was 42.0%(87/208).The expression of PTPN12 was correlated with T stage(?~2 = 46.175,P = 0.000),lymph node metastasis(?~2 = 25.444,P = 0.000)and clinical stage(?~2 = 16.227,P = 0.000),the difference was statistically significant(P <0.05),but not with age(?~2 = 0.377,P = 0.539)and pathological type(?~2 = 5.614,P = 0.114),the difference was not statistically significant(P> 0.05).4 The expression of EGFR and PTPN12 protein was significantly correlated with the expression of EGFR and PTPN12 protein.(?~2 = 8.431,P =0.004,rs =-0.200)5 The positive expression rate of EGFR was 69.2%,the positive expression rate of CK5 / 6 was 59.6%,the expression of EGFR was positively correlated with CK5 / 6(rs = 0.377,P = 0.000),and the difference was Statistically significant(P <0.05).6 The effect of PTPN1 expression on the survival of patients with breast cancer was assessed using Kaplan-Meier and Log-rank tests.Analysis showed that the overall survival rate was lower in patients with PTPN1 overexpression(?~2 = 14.129,P = 0.000)compared with PTPN1 low expression.The survival time of PTPN1-negative patients was higher than that of PTPN1-positive patients,and the difference was statistically significant(P <0.05).7 The Kaplan-Meier and Log-rank tests were used to assess the effect of PTPN12 expression on the survival of patients with breast cancer.The overall survival rate of patients with high expression of PTPN12(?~2 = 26.522,P =0.000).The difference between the two groups was statistically significant(P<0.05).The survival rate of patients with PTPN12 expression was lower than that of PTPN12(P <0.05).8 The results of single factor regression showed that the age and pathologic type had no effect on the overall survival of the patients(P> 0.05).The expression of TTP,lymph node metastasis,TNM stage,PTPN1 expression and PTPN12 expression had a significant effect on the overall survival of the patients(P<0.05).Univariate analysis showed that T stage,lymph node metastasis,TNM staging,PTPN1 and PTPN12 expression were correlated with prognosis.9 Multivariate regression analysis showed that there was no significant difference in survival period between patients with T stage,lymph node metastasis and TNM staging(P>0.05).However,the expression of PTPN1 and PTPN12 had a significant effect on the overall survival of the patients,the difference was statistically significant(P<0.05).Conclusions:1 The expression of PTPN1 was not associated with age and pathology of patients,but was positively correlated with stage T,lymph node metastasis and TNM staging.The mean survival time of PTPN1 high expression group was shorter than that of low expression group.PTPN1 positive expression is an independent prognostic factor that affects the overall survival of the patient.PTPN1 may be a potential target for the treatment of anti-triple negative breast cancer.2 The expression of PTPN12 was not related to the age and pathologic type of the patients,but negatively correlated with T stage,lymph node metastasis and TNM staging.PTPN12 expression was negative in patients with a shorter survival time than patients with positive PTPN12 expression.PTPN12 as a tumor suppressor gene,its positive expression and triple negative breast cancer patients with poor prognosis was negatively correlated.3 EGFR was highly expressed in triple-negative breast cancer and had a significant negative correlation with PTPN12 protein expression.PTPN12 had a negative effect on EGFR and was the target of PTPN12.