| Objective: 1.The relationship between the expression of androgen receptor(AR)in breast cancer tissues and pathological features was analyzed to explore the predictive value of AR in breast cancer prognsis.2.To study the effect and mechanism of androgen receptor on breast cancer cell line.Method: 1.144 breast cancer patients were selected,and surgical pathological tissues were collected.Immunohistochemical methods were used to detect the expression characteristics of Androgen receptor(AR),Estrogen receptor(ER),Progesterone Receptor(PR),Human epidermal growth factor receptor 2(HER-2)and Ki-67 in breast cancer tissues.Collect the general information and clinicopathological parameters of breast cancer(molecular typing,T stage,N stage,clinical stage,lymph node metastasis,histological grade,neurovascular invasion,etc.)through the medical record system.Disease free survival(DFS)and overall survival(over survival,OS)were observed,the end point of follow-up was Dec 2020.2.MCF-7(ERα,ERβ,AR positive)and MDA-MB-453(ERα negative,ERβ positive,AR positive)were selected as experimental cells.Dihydrotestosterone(DHT)was used as an AR agonist,and Enzalutamide(Enza)was used as an AR inhibitor.CCK8 detection kit was used to analyze the cell proliferation levels after drug treatment,and the expression levels of AR and P21 were detected by PCR and Western Blot.CCK8 assay was used to detect the proliferation activity of cells.Results: 1.(1)The average age of the subjects was 52.2 ± 8.8 years,and 78 patients had lymph node metastasis,accounting for 54.1%.The proportion of clinical stage I to III was 20.1%,43.1% and 36.8%.Molecular typing: The proportions of Luminal A,Luminal B,HER-2 overexpression and triple negative breast cancer(TNBC)were 22.9%,51.4%,6.3%,and 19.4%,respectively.Histological classification: G1,G2,and G3 accounted for 18.0%,64.6%,and 17.4%.(2)Immunohistochemical detection results: 85 cases were AR positive,the positive rate was 59.0%,59 cases were AR negative,accounting for 41.0%.The proportions of ERpositive,PR-positive,HER2-positive,and Ki-67 ≥ 14% were 67.4%,64.6%,25.7%,and 47.2%,respectively.(3)There was no statistical correlation between AR expression and age,histological grade,neurovascular invasion,PR expression,HER-2 expression,Ki-67 expression(P>0.05).The AR positive rate of tumors with a diameter of less than 2cm is higher than ≥2cm(73.9% VS 52.9%).The AR positive rate of tumors in stages I to II is higher than that of III(65.9% VS 56.3%).The positive rate of AR in lymph node metastasis-positive tumors was lower than that in negative patients(51.3% VS 59.2%),and the positive rate of AR in ER-expressing tumors was higher than that in ER-negative tumors(69.1% VS 38.3%).There was no statistical difference in AR-positive rates among different molecular types of breast cancer(P <0.05).(4)DFS and OS were significantly better in AR positive patients than those in AR negative patients(P <0.05),but the Cox hazard ratio regression analysis showed that AR was not an independent predictor of DFS and OS in breast cancer patients.Tumor diameter,lymph node infiltration,ER expression,and Ki-67 expression were independent predictors of disease-free survival time(P <0.05).Age,lymph node infiltration,tumor diameter,ER expression,and Ki-67 expression were independent predictors of overall survival(P <0.05).2.(1)Fluorescence quantitative assay showed that the expression of AR m RNA in MDAMB-453 cells was about 6.3 times that in MCF-7 cells.(2)DHT 1 n M promoted the growth of MCF-7 and MDA-MB-453 cells,and Enza 10 μM significantly inhibit the growth of MCF-7 and MDA-MB-453 cells.(3)The results of Q-PCR and Western Blot assay showed that the expression levels of AR m RNA and protein in MCF-7 and MDA-MB-453 cells were significantly increased after DHT treatment(P <0.05),while the expression levels of AR m RNA and protein were significantly decreased after Enza treatment,which were lower than those in the control group(P <0.05).(4)The results of Q-PCR and Western Blot showed that the changes of AR expression affected the expression of P21 m RNA and protein,thus affecting the proliferation activity of cells.Conclusions: 1.(1)AR-positive breast cancer is less invasive and malignant,which can indicate the state and stage of disease progression and can be used as a molecular target for breast cancer;(2)The expression level of AR was higher in ER positive breast cancer,suggesting a synergistic effect between the two;(3)AR expression may suggest a better long-term prognosis,but it is not an independent predictor of patient prognosis.2.(1)AR is expressed in different breast cancer cells with different level of expression.(2)The m RNA and protein levels of AR were inhibited by Enza.(3)DHT can promote AR on m RNA and protein levels.(4)The change of AR expression affects cells proliferation,and its proliferation may be through the effect on P21. |
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