The Relationship Between Expression Of RSK4 Or LOX Of Breast Cancer With Axillary Lymph Node Metastasis

Part 1 Expression of P90 ribosomal S6 kinase 4 and lysyl oxidase in breast cancer and its clinical significanceObjective: The study was aimed to investigate the effect of RSK4 and LOX on invasion and metastasis in breast cancer and its clinical significance.Methods: The expression of RSK4 and LOX protein in paired 227 cases of human breast cancer, adjacent normal tissue were detected by S-P immunohistochemistry. Correlation of RSK4 or LOX expression with clinicopathologic characteristic was evaluated in breast cancer tissues.Results: RSK4 expression in 227 breast cancer tissues(39.6%, 90/227) were lower than those in paired adjacent noncancerous tissuesn(72.7%, 165/227). There is a significant statistical difference(χ2=50.325, p<0.01). RSK expression was related with in breast caner histological differentiation(χ2=6.668, p=0.036), primary tumor size(χ2=29.018, p<0.01), axillary lymph node metastasis(χ2=9.635, p=0.022) and clinical stage(χ2=28.666, p<0.01), while there was no relation between RSK4 expression with age(χ2=0.239, p=0.625), menopause(χ2=0.017, p=0.897), body mass index(BMI)(χ2=1.115, p=0.291), ER(χ2=0.178, p=0.673), PR(χ2=0.750, p=0.386), HER2 status(χ2=2.184, p=0.139) and molecular subtyping(χ2=1.468, p=0.850). LOX expression was significantly higher in breast cancer(64.8%, 147/227) than adjacent tissues(31.7%, 72/227)(χ2=49.621, p<0.01). LOX expression was related with in breast caner histological differentiation(χ2=8.312, p=0.016), primary tumor size(χ2=6.183, p=0.045), axillary lymph node metastasis(χ2=10.597, p=0.014), clinical stage(χ2=7.950, p=0.019), ER(χ2=19.731, p<0.01), PR(χ2=5.221, p=0.022) and HER2(χ2=16.648, p<0.01), while there was no relation between LOX expression with age(χ2=0.779, p=0.377), menopause(χ2=0.633, p=0.426), BMI(χ2=0.276, p=0.599) and molecular subtyping(χ2=8.469, p=0.076).Conclusions: The results indicate that the expression of RSK4 protein is involved in the invasion and metastasis of breast cancer, which may be a suppressor gene. LOX is relevant with the occurrence of breast cancer. The degree of malignancy is higher and facilitates metastasis occurred which LOX is expressed, which may have a bad prognosis. Both RSK4 and LOX are involved in the process of breast cancer carcinogenesis and progression and play different roles.Part 2 The correlation with expression of RSK4, LOX, Cyclin D1, Ki-67,CXCR4 and E-cadherin in breast cancer with axillary lymph node metastasisObjective: The study was aimed to investigate the effect of RSK4 and LOX on breast cancer axillary lymph node metastasis and its mechanism.Methods: The expression of RSK4, LOX, Cyclin D1, Ki-67, CXCR4 and E-cadherin protein in paired 227 cases of human breast cancer, adjacent normal tissue were detected by S-P immunohistochemistry. The expression of RSK4 and LOX protein in 131 cases of metastatic lymph node tissues and 96 cases of chronic inflammatory lymph node tissues. The relationship of RSK4 or LOX expression between them in breast cancer tissues and in corresponding lymph node tissues was explored. Further, correlation of RSK4 or LOX expression with the expression of Cyclin D1, Ki-67, CXCR4 and E-cadherin was comparatively evaluated in breast cancer tissues with or without axillary lymph node metastasis.Results: The expression of RSK4 protein shew significant negative correlaiton(r=-0.235, p<0.01) and the expression of LOX protein shew significant positive correlation(r=0.199, p<0.01) with the number of axillary lymph node metastasis. RSK4 expression in metastatic lymph node tissues(33.6%, 44/131) were lower than those in chronic inflammatory lymph node tissues(82.3%, 79/96). There is a significant statistical difference(χ2=53.937, p<0.01). LOX expression in metastatic lymph node tissues(72.5%, 95/131) was significantly higher than chronic inflammatory lymph node tissues(14.6%, 14/96)(χ2=74.499, p<0.01). The correlation analysis showed both the expression of RSk4 protein(r=0.593, p<0.01) and the expression of LOX protein(r=0.188, p=0.031) in breast cancer tissues and in metastatic lymph node tissues was consistent with in breast caner with axillary lymph node metastasis, and the difference was statistically significant. But both the expression of RSK4 protein(r=-0.062, p=0.548) and the expression of LOX protein(r=-0.191, p=0.063) in breast cancer tissues had no correlation with those in chronic inflammatory lymph node tissues. The RSK4 protein shew significant negative correlation with the LOX(r=-0.559, p<0.01), Cyclin D1(r=-0.466, p<0.01), Ki-67(r=-0.486, p<0.01) and CXCR4(r=-0.384, p<0.01) protein expression in breast cancer, but shew significant positive correlation with the E-cadherin(r=0.535, p<0.01) protein expression. The LOX protein shew significant positive correlation with the Cyclin D1(r=0.476, p<0.01), Ki-67(r=0.492, p<0.01) and CXCR4(r=0.539, p<0.01) protein expression, but shew significant negative correlation with the E-cadherin(r=-0.387, p<0.01) protein expression in breast cancer.Conclusions: RSK4 is a breast cancer suppressor gene. The low or abnormal expression of RSK4 protein is associated with metastasis of breast caner, while the over expression of LOX protein promote development, invasion and metastasis of breast cancer. The mechanism may be related to Cyclin D1, Ki-67, CXCR4 and E-cadherin abnormal expression.