The Retrospective Cohort Study Of SCUBE3 Protein Expression And The Therapy Efficacy In Breast Cancer

Background:Breast cancer is one of the most common malignancies in women.Although there are many traditional clinical pathological prognostic indicators,and there are many treatments such as surgery,radiotherapy and chemotherapy,but because of its high heterogeneity,there is still a high risk of metastasis and death.SCUBE3 is an endogenous transforming growth factor-? receptor ligand and has been shown to regulate the epithelial-mesenchymal transition and angiogenesis to promote cancer progression.Therefore,we hypothesized that elevated expression of SCUBE3 may increase the risk of metastasis or death in breast cancer patients and may have an impact on the prognosis of patients receiving radiation therapy.It will provide scientific evidence for finding new prognostic molecular markers and new therapeutic targets.Methods:A retrospective analysis of 137 women with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province was performed at a median follow-up of 121(26-132)months.A retrospective collection of 247 women with breast cancer who underwent surgical resection in Shenzhen Second People's Hospital was performed at a median follow-up of 72(10-100)months.Immunohistochemistry was used to detect the expression of SCUBE3 in cancer tissues,and COX multiple regression and interaction test were used to analyze whether there was an interaction between SCUBE3 and the prognosis of patients for prognosis in Taizhou Hospital of Zhejiang Province,the patients of Shenzhen Second People's Hospital and the two groups of patients.Result:1.Follow-up results: The disease-free survival of patients in Taizhou Hospital of Zhejiang Province was 10 to 132 months,with a median of 119 months and 27.7%(38/137)with local recurrence and/or distant metastasis;the overall survival was From March to December,the median was 121 months and the mortality rate during follow-up was 21.2%(29/137).The disease-free survival of patients in Shenzhen Second People's Hospital was 4 to 100 months,with a median of 72 months and 11.3%(28/247)with local recurrence and/or distant metastasis;the overall survival was 10 to 100.The median was 72 months and the mortality rate during the follow-up period was 3.6%(9/247).2.The relationship between SCUBE3 protein expression and clinicopathological features: According to the data analysis of Zhejiang Taizhou People's Hospital,the distribution of SCUBE3 high expression group and low expression group was different in pathological grade and pathological type(P<0.05).No significant differences were found among patients in Shenzhen Second People's Hospital.According to the data of the combined population,the SCUBE3 high expression group and the low expression group had differences in age,pathological grade,PR expression,and molecular subtype distribution(P<0.05).The comprehensive analysis results suggest that there may be a significant correlation between SCUBE3 protein expression level and pathological grade.3.The relationship between the expression of SCUBE3 and the risk of recurrence and metastasis: According to the single factor analysis and COX multiple regression analysis of patients from Zhejiang Taizhou Hospital,Shenzhen Second People's Hospital,and COX multiple regression analysis,the relationship between SCUBE3 expression and recurrence risk Not statistically significant.4.The relationship between the expression of SCUBE3 and the risk of death:In the patients and combined population of Taizhou Hospital in Zhejiang Province,the SCUBE3 immunohistochemical scores had significant effects on mortality risk during the follow-up period(132 months)(HR>1,P<0.05).In Shenzhen Second People's Hospital,this phenomenon may not be observed due to the low incidence of death time(9/348,3.6%).This suggests that the higher the SCUBE3 score,the higher the risk of death.After adjusting for confounding factors by stepwise COX multiple regression,the SCUBE3 immunohistochemical score of Taizhou Hospital in Zhejiang Province has a significant predictive effect on mortality risk.For each increase in SCUBE3 immunohistochemical score,the risk of death will increase by 14%(95% CI: 1.01-1.28,P=0.0351).This independent predictive effect remained in the pooled population(P < 0.05).This demonstrates that SCUBE3 expression is an independent predictor of breast cancer mortality risk.5.Interaction between SCUBE3 and treatment: There is an interaction between the expression of SCUBE3 and the effect of radiotherapy on prognosis(no disease survival)(interacting P value = 0.0125),but the expression of SCUBE3 and chemotherapy,endocrine therapy,anti-HER-2 The interaction of treatment on prognosis was not significant(P>0.05).In the subgroup of radiotherapy,after adjusting for the influence of the mixed factors,the SCUBE3 expression score increased by 1% for each point,and the risk of recurrence and metastasis increased by 40%(HR 1.40,95% CI 1.02-1.93,P=0.0145).Conclusion:1,SCUBE3 can be used as an independent prognostic indicator of breast cancer.The higher the expression of SCUBE3,the higher the risk of death in breast cancer patients.2.There is an interaction between SCUBE3 and the effect of radiotherapy on prognosis.Among patients receiving radiation therapy,SCUBE3 is elevated and the risk of metastasis is significantly elevated.SCUBE3 may be a potential predictor of adjuvant radiotherapy for breast cancer.