| Objective:The aim of this study is to detect the expression of SUMO activating enzyme subunit 1(SAE1)in triple negative breast cancer(TNBC)tissues and the influence on the prognosis of TNBC patients.Methods:We downloaded a total of 558 cases of TNBC tissues and normal tissues from The Cancer Genome Atlas(TCGA)database and GEO(Gene Expression Omnibus)database.R language software(http://bioconductor.org/bioc Lite.R version 3.5.0)was used to analyze the chip data of GEO data sets(GSE21653,GSE31448,GSE45827,GSE53752,GSE65216,GSE36295,GSE37751,GSE38959,GSW61724)and TCGA database.207 cases of primary TNBC with complete clinical data,clear diagnosis were collected from Fujian Medical University Union Hospital from June 2013 to May 2018.Clinical data of TNBC patients were collected,including age,time of admission,type of surgery,tumor size,tumor grade,lymphovascular invasion,lymph node metastasis,time of recurrence or metastasis,time of death,and cause of death.The end of follow-up was December 31,2020.The expression of SAE1 in TNBC tissues was detected by immunohistochemical staining method.SAE1 was scored semi-quantitatively,with tumor cell staining strength0-3 multiplied by a staining range of 1-4.Chi-square test,univariate analysis and multivariate analysis(Cox regression analysis)were used to determine the influence of SAE1,age,type of surgery,tumor size,histological grade,lymphovascular invasion,lymph node metastasis and other factors on the prognosis of TNBC patients.Results:(1)The chip data of GEO data sets(GSE21653,GSE31448,GSE45827,GSE53752,GSE65216,GSE36295,GSE37751,GSE38959,GSW61724)and TCGA database was analyzed by R software.The results showed that the m RNA levels of SAE1 in TNBC tissues were significantly higher than those in paired non-tumor breast tissues.(2)TNBC tissue samples were collected from 207 patients,ranging in age from 27 to 72 years old(median age: 51 years old).93 patients was ≤50 years old and 114 patients was>50 years old;86 patients was with tumor diameter ≤2cm,121 patients was with > 2cm;77 patients was with grade I +II,130 patients was with grade III;134patients had lymphovascular invasion,and 73 patients did not had lymphovascular invasion;124 patients presented no lymph node metastasis while 83 patients had lymph node metastasis;195 patients received total mastectomy and 12 patients received breast-conserving surgery.The follow-up time ranged from 7 to 78 months,with a median follow-up of 50 months.53 patients(25.6%)had tumor recurrence or metastasis,and 34 patients(16.4%)died of breast cancer.(3)SAE1 was expressed in the cytoplasm of tumor cells.The percentage of stained positive cells was scored from 1 to 4.The staining intensity score was calculated from 0to 3.The final scores were based on the multiply product of these two scores.A score>7was defined as high expression level and a score≤6 was defined as low expression..According to the scoring results,they were divided into SAE1-high expression group(SAE1-H)and SAE1-low expression group(SAE1-L).There were 78 cases of SAE1-H and 129 cases of SAE1-L.The expression of SAE1 protein in TNBC tissues was significantly higher than that in adjacent tissues.There was no statistically significant difference in SAE1 expression among different groups of age,tumor size,histological grade,lymphovascular invasion,lymph node metastasis,and surgical methods(P >0.05).(4)Univariate regression analysis showed that age,tumor size,histological grade,lymphovascular invasion,lymph node metastasis and high SAE1 expression were correlated with disease-free survival(DFS)of patients with TNBC(P < 0.05).There was no significant correlation between type of surgery and disease-free survival(DFS)(P >0.05).Histological grade,lymph node metastasis and high expression of SAE1 were correlated with overall survival(OS)(P < 0.05).There was no significant correlation between age,tumor size,lymphovascular invasion,type of surgery and overall survival(OS)(P ≥ 0.05).(5)Multiariate analysis showed that tumor size,lymphovascular invasion,lymph node metastasis,and high expression of SAE1 were independent influencing factors for disease-free survival(DFS)of TNBC patients(P < 0.05).Histological grade,lymph node metastasis and high expression of SAE1 were independent influencing factors for overall survival(OS)of TNBC patients(P < 0.05).Conclusion:(1)The levels of SAE1 in TNBC tissues were significantly higher in tumor tissues than those in paired non-tumor breast tissues at the chip data of GEO data sets(GSE21653,GSE31448,GSE45827,GSE53752,GSE65216,GSE36295,GSE37751,GSE38959,GSW61724)and TCGA database.(2)The expression of SAE1 protein in TNBC tissues was significantly higher than that in adjacent tissues.(3)There was no significant difference in the expression of SAE1 among different groups including age,tumor size,histological grade,lymphovascular invasion,lymph node metastasis,and type of surgery(P > 0.05).(4)The high expression of SAE1 is a risk factor for tumor recurrence or metastasis and overall survival for TNBC patients.SAE1 can be used as an indicator for the prognosis of triple negative breast cancer. |
