| Background:In recent years,with the development of breast cancer molecular classification,know more about breast cancer genome,which is inside the breast cancer is highly heterogeneous,by a variety of subtypes of a class of diseases.Triple-negative breast cancer(TNBC)as a kind of special phenotype breast cancer,because of its aggressive,high incidence of recurrence and metastasis,and after recurrence and metastases the treatment effect is poor,has been widespread concern and research.High mobility group box 1(HMGB1)is a non-histone chromosome nucleoprotein,which can be combined with DNA to form a nuclear protein complex,which plays an important role in gene expression regulation.HMGB1 expression levels in breast cancer tissue higher than normal tissue,and high expression in late clinical stage?high histological grade?lymph node metastasis and distant metastasis,suggesting that the biological behavior of invasion and metastasis of breast cancer,HMGB1 may play an important role.Toll-like receptors(TLRs)has highly stable molecular structure,it is an important pattern recognition receptors which are expressed in human epithelial cells and immune cells.TLRs can identifying the combination of different pathogen-associated molecular patterns,perceive the invasion of pathogenic bacteria,activate a series of cell signal transduction,release of inflammatory medium,it plays an important role in the activation of innate immunity and acquired immune defense.TLR4 is an important member of TLRs,which plays an important role in promoting tumor cell proliferation and resistance to apoptosis and enhancement of tumor cell invasiveness.TLR4 is a major TLR subtypes of breast cancer tissues,and TLR4 expression positive breast cancer patients' overall survival and disease-free survival rates were significantly lower than TLR4 expression negative,heralded the TLR4 expression may has closely related with invasion and metastasis of breast cancer.Epidemiological studies about breast cancer has a long history,but most of studiesEpidemiological studies about breast cancer has a long history,but most of studies regard the breast cancer as a disease to analyze the risk,without considering the different subtypes of breast cancer risk might be different.Different molecular classification of breast cancer with its high rates of different age groups,there are significant difference risk factors in different subtypes of breast cancer,indicating that the TNBC may have different epidemiology characteristics compare with other subtypes of breast cancer.Objective:1?Experimental Study: Through experimental study,discussion the differences expression levels of HMGB1 and TLR4 in TNBC and non-TNBC tissues,further analysis the correlation between expression of HMGB1/TLR4 with TNBC clinicopathological features and prognosis.2?Epidemiological investigation: Through epidemiological investigation,discuss the main risk factors for TNBC,which provided basis for the risk assessment of TNBC and the decrease of risk.and the decrease of risk.Method:1?Experimental research section: Collection the patients of First Affiliated Hospital of Fujian Medical University,whose without neoadjuvant therapy and underwent surgical resection by the pathological diagnosis to TNBC,treated as the experimental group,from 2011 year to 2013 year.By 1:2 randomly paired collected over the same period Non-TNBC as a control group of patients.By the method of immunohistochemical staining,detection of the experimental group and control group of HMGB1/TLR4 expression in paraffin-embedded tissue sample,and through statistical methods to analyze the relevance of its expression and clinicopathological features.2?Epidemiological survey section: Collected from January to June in 2017 year new-onset invasive breast cancer patients as the study group,according to immunohistochemical results are divided into groups TNBC and non-TNBC group.By 1: 2 pairing collected over the same period outpatient healthy people as a normal control group,collected breast cancer risk factors of the study group and the control group related information,and risk factors Logistic regression analysis.Result: Result: 1?The positive expression rates of HMGB1 and TLR4 in TNBC group were significantly higher than non-TNBC group(81.4% VS 64%;69.8% VS 51.2%),the difference was statistically significant(P<0.05).2?The relationship between HMGB1/TLR4 expression and clinical pathology in TNBC group: High histological grade ? lymph node metastasis ? Ki-67 high expression and so on was highly correlated with the positive degree of HMGB1/TLR4,the difference was statistically significant(P<0.05).In postoperative recurrence aspect,with DFS?36 months the positive rate was were 94.4%,DFS>36 months the positive rate was 80%,the difference was statistically significant(P<0.05).3?Single factor Logistic regression analysis of risk factors and TNBC was positively correlated variables:high BMI?early menarche?estrogen replacement therapy?negative events?work pressure? mental illness and family history of breast cancer;and long breastfeeding?exercise frequency>3 times/week is negatively correlated variables.Multivariate Logistic regression analysis showed that independent risk factors for TNBC: estrogen replacement therapy?high BMI?negative life events?mental illness and family history of breast cancer;breast-feeding for?12 months,exercise frequency>3 times/week is an independent protective factor of TNBC.Conclusion: 1?The high expression of HMGB1/TLR4 is related to the high invasion characteristics of TNBC.HMGB1/TLR4 high expression of TNBC patients are often associated with the clinical features of high histological grade?lymph node metastasis and high Ki-67 expression,and has poor clinical prognosis.2?The independent risk factor for TNBC is estrogen replacement therapy?high BMI?negative life events? mental illness and family history of breast cancer. |
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