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Study On The Correlation Between TSP50Expression And Metastasis Of Breast Cancer

Posted on:2016-11-29Degree:MasterType:Thesis
Country:ChinaCandidate:M LiFull Text:PDF
GTID:2284330467999820Subject:Pathology and pathophysiology
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Breast cancer is one of the most prevalent cancers affecting physical and themental health of the women in the world. The present study shows that multiple genesand factors are involved in breast cancer occurrence, and the imbalance expression ofoncogene and tumor suppressor genes plays key role in the occurrence and metastasisof breast cancer. With the deepening of the people in breast cancer biology behaviorresearch,has found a variety of breast cancer related genes, including TSP50breastcancer gene is a newly discovered in recent years.TSP50is a specific expression ofprotein, testicular reports in ovarian cancer, stomach cancer, colon cancer, kidneycancer and throat cancer, and other abnormal high expression in malignant tumor.Ourprevious studies have found that TSP50also presents high expression in breast cancertissue, and in vitro studies have found,members of our research group found that theWith the deepening of the people in breast cancer biology behavior research, hasfound a variety of breast cancer related genes, including TSP50breast cancer gene is anewly discovered in recent years.TSP50is a specific expression of protein, testicularreports in ovarian cancer, stomach cancer, colon cancer, kidney cancer and throatcancer, and other abnormal high expression in malignant tumor.Our previous studieshave found that TSP50also presents high expression in breast cancer tissue, and invitro studies have found NF-kappaB-mediated activation of P65and expression ofMMP9in normal human breast MCF-10A and breast cancer MDA-MB231cells.Here, we measured expression of TSP50, p65and MMP9in breast cancer tissuesanalyzed its clinical significance to further confirm whether TSP50promote breastcancer tumorigenesis and metastasis by activating NF-KB signaling pathway, andinvestigated the role and mechanism of TSP50in breast cancer metastasis.Methods:1.With the deepening of the people in breast cancer biology behavior research, has found a variety of breast cancer related genes, including TSP50breast cancer geneis a newly discovered in recent years.TSP50is a specific expression of protein,testicular reports in ovarian cancer, stomach cancer, colon cancer, kidney cancer andthroat cancer, and other abnormal high expression in malignant tumor.Our previousstudies have found that TSP50also presents high expression in breast cancer tissue,and in vitro studies have found immunohistochemistry in breast ductal carcinoma insite(18cases), infiltrating lobular carcinoma(10cases),infiltrating ductal carcinoma(150cases), infiltration ductal carcinoma accompanied by micro papillarycarcinoma (14cases), breast adenosis(36cases)and analyze its correlationwith clinical parameters.2.By Western blot and RT-PCR method, we detected the expression levels ofTSP50,p65and MMP9in lymph node metastasis group(7cases), without lymphnode(7cases) metastasis infiltrating ductal carcinoma and adjacent breast tissue (7cases).3. Analysis of TSP50, MMP9, P65levels in various types of breast carcinomaand studies the association of TSP50, MMP9, P65levels with ER, PR, HER-2,mtP53and Ki67levels.4.Application of SPSS17.0statistical analysis software for statistical analysis.Results:1.The positive expression rates of TSP50in the breast ductal carcinoma in site,infiltrating ductal carcinoma, infiltration ductal carcinoma accompanied by micropapillary carcinoma,infiltrating lobular carcinoma were77.8%and82.7%,100%,80.0%respectively, which was significantly higher than that in breast adenosis(P1<0.05,P2<0.001,P3<0.001,P4<0.01)。TSP50expression in lymph nodemetastasis group was significantly higher than that without lymph node metastasis (P<0.05), and TSP50expression in tumors larger than2.0cm group was significantlyhigher than that less than2.0cm group (P<0.001), and there was no significantcorrelation with pathological grading(P>0.05).2.The positive expression rates of P65in the breast ductal carcinoma in site, infiltrating ductal carcinoma, infiltration ductal carcinoma accompanied by micropapillary carcinoma,infiltrating lobular carcinoma were50.0%and91.3%,100%70.0%respectively, which was significantly higher than that in breast adenosis5.6%(P1<0.001,P2<0.001,P3<0.001,P4<0.001). P65expression in lymph nodemetastasis group was significantly higher than that without lymph node metastasis (P<0.01), and there was no significant correlation with pathological grading and tumorsize (P1>0.05,P2>0.05).3.The positive expression rates of MMP9in the breast ductal carcinoma in site,infiltrating ductal carcinoma, infiltration ductal carcinoma accompanied by micropapillary carcinoma,infiltrating lobular carcinoma were66.7%and92.7%,100%70.0%respectively, which was significantly higher than that in breast adenosis66.1%(P1<0.01,P2<0.001,P3<0.001,P4<0.01). MMP9expression in lymph nodemetastasis group was significantly higher than that without lymph node metastasis (P<0.05), and MMP9expression in tumors larger than2.0cm group was significantlyhigher than that less than2.0cm group (P<0.001), and there was no significantcorrelation with pathological grading (P>0.05).4.In the breast invasive ductal carcinoma, the expression of TSP50waspositively correlated with P65and MMP9(r>0), Among the breast invasive ductalcarcinoma,116cases were positive for TSP50, MMP9and P65. Among the breastadenosis,0cases were positive for TSP50, MMP9and P65. The difference wassignificant (P<0.001). Co-expression of TSP50, p65and MMP9in lymph nodemetastasis group were significantly higher than those without lymph node metastasis(P <0.01). No significant difference in different pathological grading group andtumor size group(P>0.05).5.Western blot and RT-PCR results suggested that TSP50、 P65、 MMP9expression in the breast infiltrating ductal carcinoma significantly higher thanadjacent breast tissue,and in lymph node metastasis group was higher than thatwithout lymph node metastasis.6. Co-expression of TSP50,MMP9and P65were positively correlated with HER-2in breast invasive ductal carcinoma(r>0), and it was not correlated with ER、PR、P53and Ki67(r=0).Conclusions:1. TSP50expression may increase the occurrence and metastasis of breast cancer.through the activation of NF-B signaling pathway and expression of target proteinsMMP9.2. The positive co-expression TSP50, p65and MMP9may be associated withbreast cancer prognostic indicator HER-2, suggesting that it is expected to asindicators of prognosis and a potential therapeutic target for breast cancer.
Keywords/Search Tags:TSP50, breast cancer, P65, MMP9, NF-KB
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