Study On The Expression Of ASPH And CD109 In Breast Cancer Tissue Samples

Background and objectiveBreast cancer,which has high morbidity and mortality,is one of the most common high-heterogeneity tumors.Although the diagnosis and treatment of breast cancer have greatly improved with the development of medical standards,breast cancer remains the main factor for the death of women worldwide.There are still certain risks and disadvantages in the treatment of breast cancer,such as easy recurrence,metastasis,tumor resistance,and toxic side effects.Therefore,screening and determination specific biomarkers of breast tumors is very important,which will help the initial diagnosis of breast cancer,prognosis and select targeted therapeutic targets for patients.ASPH(aspartate β-hydroxylase)participates in cell movement and differentiation by catalyzing the post-translational hydroxylation of aspartic acid and asparagine residues in epidermal growth factor-like domains(EGFDs),and participates in various signaling pathways.Recent studies have shown that ASPH plays an important role in the pathogenesis of certain malignant diseases in humans,including breast cancer,but whether it can be used as an independent prognostic factor for breast cancer is still controversial.So far,the role of ASPH in the pathogenesis of breast cancer patients is still unclear,and further study by scientists is needed.In this study,the role of ASPH in breast cancer was initially studied by exploring the relationship between clinical parameters and ASPH expression.In this study,the role of ASPH in breast cancer was initially studied by exploring the association between clinicopathological features and ASPH expression.Cluster of differentiation 109(CD109)as a TGF-β co-receptor plays a key role in the pathogenesis of certain malignant tumors.The latest research shows that CD109 can promote tumor cells invasion and metastasis through JAK-STAT3 and EGFR-AKT-mTOR pathways.However,the function of CD109 in tumorigenesis and carcinogenesis of breast cancer remains unclear.In this study,we verified the function of CD109 in breast cancer by exploring the association between clinicopathological features and CD109 expression.MethodsTissue samples were surgically excised of breast cancer patients,which used to detect the expression of protein using the methods of immunohistochemical staining and western blot and detect the expression of mRNA using the methods of qRTPCR.Then,Analyze the association between ASPH and CD109 expression and clinicopathological characteristics.Finally,data were obtained from Oncomine database to explore the correlation between mRNA expression and breast cancer molecular typing and pathological stage.Use the GEPIA database to explore the relationship between ASPH expression and prognosis.Experimental resultsPart Ⅰ: Obtain the patient’s clinical information from the patient’s electronic medical record,and combine the results of this experiment to statistically analyze the relevant data.The results showed that in the sample tissues of 68 breast cancer patients,the positive expression of ASPH protein accounted for 83.33% in tumor tissues,while the proportion in adjacent normal tissues was 35.71%.In addition,compared with in situ carcinoma ASPH protein has a strong expression in invasive breast cancer.There is no significant correlation between the distribution of ASPH expression intensity with and age(P = 0.249),cancer type(P = 0.935),molecular type(P = 0.484),ER(P = 0.847),PR(P = 0.683),HER-2(P = 0.457)),Ki-67(P = 0.147),p63(P = 0.988),CK5 / 6(P = 0.598)and EGFR(P = 0.41),but it is associated with lymphatic metastasis(P = 0.006),Tumor size(P = 0.004),TNM stage(P = 0.000)and other indicators were significantly correlated(P <0.05).Western blot results of 9 breast cancer patients’ fresh tissues(breast cancer tissues and adjacent tissues)also confirmed that ASPH protein expression was associated with tumor clinical TNM stage(P <0.05).Oncomine database analyzes the relationship between ASPH mRNA expression and breast cancer types,tumor clinical TNM stage and molecular typing and other pathological indicators.The results show that the expression of ASPH mRNA in invasive breast cancer is compared between invasive breast cancer and orthotopic breast cancer.The medium expression level is higher,and the expression level of ASPH mRNA in each TNM stage of the tumor is significantly different,but the expression level in different molecular subtypes is not much different.Analysis of the ASPH gene expression in 1070 breast cancer samples in the GEPIA database found that the overall survival of patients with high ASPH expression was worse than that with low ASPH expression.In conclusion,the overexpression of ASPH is closely related to the pathological stage and poor prognosis of breast cancer patients.It is speculated that ASPH is involved in regulating the development of breast cancer with E-cadherin through the epithelial-mesenchymal transition pathway,which may be a potential biomarker for early diagnosis,prognosis and target therapy.Part II: The results of immunohistochemical in samples of 70 breast cancer patients showed that the expression distribution of CD109 protein had no significant correlation with age(P = 0.193),cancer type(P = 0.142)and axillary lymphatic metastasis(P = 0.169),and the indicator of tumor size(P = 0.001),distant lymphatic metastasis(P = 0.011),TNM staging(P = 0.002)molecular typing(P = 0.000),ER(P = 0.010),PR(P = 0.045),HER-2(P = 0.031))and EGFR(P = 0.022)had a significant correlation(P <0.05).Western blot results of fresh tissues(breast cancer tissues and adjacent tissues)from 12 breast cancer patients showed that the expression of CD109 protein was correlated with breast cancer TNM stage and molecular subtype(P <0.05).Oncomine database analysis results indicate that the high expression of CD109 mRNA is related to the highly aggressive phenotype of advanced tumors.In short,CD109 has a higher expression level in some breast cancers with poor prognosis and high prone to metastasis,and is involved in the proliferation and metastasis of breast cancer.Therefore,it is suggested that CD109 may be an auxiliary marker for early diagnosis of breast cancer with high malignancy such as triple negative or basal-like type as well as a potential therapeutic target for anti-cancer drugs.