To Explore The Correlation Between TCM Constitution And Recurrence And Metastasis Of Triple-negative Breast Cancer Based On MiRNA Difference

Objective:To observe the factors,such as TCM constitution,patients' general information,tumor characteristics,past treatment methods,which is related to local recurrence and metastasis of triple-negative breast cancer,and build a risk assessment model for recurrence and metastasis of triple-negative breast cancer.To explore the differences of miRNA expression in different TCM physique groups.Methods:This study included 159 cases of postoperative patients with triple-negative breast cancer.Collected the patients' general information(including age,BMI,occupation,cultural level,family history),tumor pathology characteristics(including tumor size,histological grade,lymph node metastasis,the presence of vascular tumors,Ki67),previous treatment(including surgery method,radiotherapy,chemotherapy.Chinese medicine treatment,interruption of treatment)and traditional Chinese medicine constitution classification within 1 after surgery.?2 analysis was used to analyze the composition of the different subgroups.Kaplan meier and Cox correlation analysis was used to analyze the related factors of recurrence and metastasis of triple-negative breast cancer after their operations,and build a risk assessment model.Collecting patients' peripheral blood with different constitutions of traditional Chinese medicine(related to recurrence and metastasis of postoperative patients with triple-negative breast cancer),each group choose 3 cases.HiSeq library sequencing technology was used to detect the differences of miRNA expression of patients with different TCM constitutions,and explore the polymorphism of epigenetic information between different TCM individuals.Results:1.The study include 159 patients with triple-negative breast cancer,they are mainly concentrated in 40?60 years old(68.8%).Among them,biased constitution is in the majority,with a proportion of 87.2%.There were more patients with Qi-deficiency and Qi-deficiency constitution,with a proportion of 24.8%and 14.2%.2.8 patients lost during the follow-up,27 patients occurred end-event.9 patients showed pulmonary metastasis,with a proportion of 33.33%,7 patients showed lymph node metastasis,with a proportion of 22.22%,5 patients showed liver metastasis with a proportion of 18.51%,3 people showed bone metastases,with a proportion of 11.11%,4 patients showed breast recurrence in situ,with a proportion of 14.83%.The recurrence rate was 7.3%in 1 year,11.9%in 2 years and 17.9%in 3 years.3.Kaplan meier survival curves showed that physical survival curves of patients with Qi-deficiency or Blood-stasis constitution was lower than those with other seven kinds of constitution,explain patients with Qi-deficiency or Blood-stasis constitution has the lower DFS and poorer prognostic than patients with other seven kinds of constitution.4.Among the patients with prolonged biased constitutions,the proportion of interrupters(34.3%)was more than those of non-interrupters with treatment of TCM(16.9%),and the difference was statistically significant.5.Single factor correlation analysis showed that family history,tumor size,lymph node metastasis,vascular tumor thrombus,timing of TCM treatment,Qi-deficiency constitution,Blood-stasis constitution were related to the recurrence and metastasis of patients with three-triple negative breast cancer 3 years after their surgeries.Lymph node metastasis,vascular tumor thrombus,Chinese medicine treatment(sequential therapy)were independent prognostic factors to predict the risk of recurrence and metastasis of patients with three-triple negative breast cancer after surgery.Lymph node metastasis,vascular tumor thrombus were risk factors,HR 2.855?4.862,respectively,sequential therapy of TCM was a protective factor,HR 0.342.The final risk assessment equation of recurrence and metastasis was obtained:h(t,X)=h0(t)exp(1.049X1+1.581X2-1.074X3).6.Comparing to the mild constitution patients,the number of upregulation miRNA of Qi-deficiency constitution patients was 16,the downregulation was 33.Differences between miRNA mainly affects the function of target genes involved in cellular water homeostasis,Rho protein signal transduction,hydrolase activity,acting on carbon-nitrogen(but not peptide)bonds,etc,which might influence the metabolic pathway of lysosomal,Notch signal pathway and MAPK signal pathway.Comparing to the mild constitution patients,the number of upregulation miRNA of Blood-stasis constitution patients was 7,the downregulation was 7.Differences between miRNA mainly affects the function of target genes involved in voltage-gated calcium channel complex,negative regulation of protein tyrosine kinase activity,etc,which might influence the metabolic pathway of lysosomal and MAPK signal pathway,p53 signaling pathway and mTOR signaling pathways,etc.Comparing to the Qi-deficiency constitution patients,the number of upregulation miRNA of Blood-stasis constitution patients was 30,the downregulation was 21.Conclusion:1.The constitution of Chinese traditional medicine might have a certain effect on the recurrence and metastasis of post-operation patients with triple-negative breast cancer.2.Treatment of Chinese traditional medicine should be early and sustained intervented to correct biased constitutions and improve the prognosis of post-operative patients with triple-negative breast cancer.3.The expression of miRNA of patients with Qi-deficiency,Blood-stasis and mild constitutions are different.Constitutions of Chinese traditional medicine may influence the prognosis of different diseases through epigenetic level.