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The Research Of Role And Mechanism Of RGS20 In The Triple Negative Breast Cancer

Posted on:2018-11-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q LiFull Text:PDF
GTID:1314330518964947Subject:Clinical Medicine
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ObjectivesBreast cancer is the most common cancer diagnosed among women and it remains the second leading cause of cancer-related mortality in women around the worldwide.Triple-negative breast cancer(TNBC)lacks expression of the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor type 2(HER2)accounts for 10-20%of the breast cancer.However,TNBC is a challenge for the treatment,due to the lacking of targeted therapy and the poor prognosis of TNBC.It is urge to find the appropriate molecular target to treat these patients.Recently,with the development and application of genomics technology,more and more researches have been carried out the construction of tumor sequencing database,some of the potential molecular that are being used in the identification of triple negative breast cancers are being explored.The aim of this study was to search,explore,and identify the possible molecular markers of triple negative breast cancer by analyzing the sequencing database of breast cancer.Method1.Analyzing the TCGA breast cancer database to screen out the TNBC specific molecular marker-RGS20 gene.2.Using the RT-PCR to detect the mRNA expression of RGS20 in the 30 pairs TNBC cancer tissues and adjacent non-cancerous tissues3.Establising the tissue microarrays(TAMs)with 86 TNBC patients'tissue samples,using the immunohistochemistry(IHC),to explore the relationship between RGS20 and clinical features.4.Analyzing of K-M plot database to explored the effect of RGS20 on prognosis of TNBC.5.Constructing the high expression of RGS20 lentiviral vector and siRNA to explored the possible mechanism of RGS20 in TNBC cell lines.Results1.According to analyze TCGA database,RGS20 was high expression in TNBC,and was high expression in lymph node positive TNBC.2.According to combined analysis of the TCGA database and RT-PCR results,the expression of RGS20 in tumor group remarkably higher than in the normal control group.3.According to analyze of Tissue microarrays of 86 TNBC patients,we found RGS20 positive group had a risk of lymph node metastasis,ki-67>14%,poor N stage and clinical stage.4.According to analyze of K-M plot database,we found the TNBC patients with higher RGS20 expression had a lower rate of RFS.5.According to the cell function experiments' results,we demonstrated that RGS20 could promote the proliferation and invasion in the TNBC cells.Conclusions1.Compared with other types of breast cancer,the high expression of RGS20 in TNBC is specific,which may be a potential molecular marker for the diagnosis of TNBC.2.RGS20 is related with lymph node metastasis in TNBC,and its high expression has poor clinical stage and higher Ki-67 percentage and worse rate of RFS,therefore,RGS20 may be a potential predictive factor for the prognosis of TNBC.3.RGS20 is highly expressed in TNBC cell lines.By regulating the expression of RGS20,we found RGS20 gene plays an important role in the proliferation and invasion of tumor cells.Therefore,RGS20 may be a potential therapeutic target of TNBC.
Keywords/Search Tags:RGS20, Triple-negative breast cancer, Lymph node metastasis, Prognosis, Proliferation, Invasion
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