Study On The Relationship Between CXCL10 MRNA Expression, Serum Protein Level And Human Breast Carcinoma

BACKGROUND CXCL10/IP-10(CXC chemokine ligand 10/ interferon-inducible protein 10) is a member of ELR(-) CXC chemokine super-family and is induced in variety of cells in response to interferon-y. CXCL10 is a potent chemoattractant for stimulated immunocyte and a potent inhibitor of angiogenesis in vivo, which is common considered as inhibitor of tumorigenesis. But, recently study found that the messenger RNA expression of CXCL10 in thyroid and colon carcinoma was more than in normal tissue, suggested that CXCL10 overexpression in carcinoma cell couldn't inhibit tumorigenesis. In our study, the expression of CXCL10 in primary breast carcinoma was significantly up-regulated than in normal tissue. Furthermore, recently study reported that Ras oncogene induced the overexpression of CXCL10 in human breast carcinoma cell lines, it had been suggested that CXCL10 may participate the tumorigenesis of breast carcinoma. However, no studies, to our knowledge, have evaluated the relationship between the expression of CXCL10 and the tumorigenesis and progression of breast carcinoma and clinical pathological factors.OBJECTIVE We analyzed CXCL10 mRNA in normal breast tissue, breast benign tumor, primary breast carcinoma and lymph node metastatic carcinoma tissues and breast cancer cell lines, and detected serum IP-10 levels in breast carcinoma patients and normal control samples, as to elucidate the relationship between CXCL10 mRNA expression, serum IP-10 levels and clinical prognostic factors of breast carcinoma, and analyze the clinical significance of diagnosis and differential diagnosis in breast carcinoma. METHODS Through quantitative real-time RT-PCR analyzed CXCL10 mRNA expression in 30 normal breast tissue,30 breast benign tumor,108 primary breast carcinoma and 30 lymph node metastatic carcinoma tissues and 8 breast cancer cell lines, by Western Blot and immunohistochemistry tested the relationship between protein and mRNA expression of CXCL10, cellular localization in breast carcinoma, we analyzed the differential expression in normal, benign and malignant breast tissues, and. Through enzyme linked immunosorbent assay(ELISA) detected the serum IP-10 levels in 44 breast carcinoma patients and 27 normal control samples, we analyzed the different levels of serum IP-10 in breast carcinoma patients and normal control, and all clinical pathological groups in breast carcinoma. We applied ROC(receiver operating characteristic curves) analysis system to evaluate the diagnostic value of CXCL10 mRNA expression and serum IP-10 levels in breast carcinoma.RESULT CXCL10 mRNA expression was significantly up-regulated in breast carcinoma tissues than in normal tissues and benign tumor (p=0.000, p=0.000) CXCL10 mRNA expression between breast primary carcinoma and LN metastatic carcinoma had no significant difference (p>0.05). CXCL10mRNA expression in ER(-) and ER(-)/PR(-) groups were higher than in ER(+) and ER(+)/PR(+) groups (p=0.037,p=0.040). The difference between Her-2(+) group and Her-2(-) group had no significance (p=0.059). CXCL10 mRNA expression in gradeⅡwas higher than in gradeⅠand gradeⅢ(p=0.034 and p>0.05,seperately). CXCL10 mRNA expression was uncorrelated with pathological sizes, lymph nodes status and clinical stage (p>0.05), and uncorrelated with 3-years disease free survival rate(p=0.130). CXCL10 mRNA expression in ER(-) breast carcinoma cell lines was higher than ER(+) cell lines, which tendency was similar with breast carcinoma tissues.The optimal operating point of the mRNA relative expression CXCL10 was 8.70E-02, which positive predictive value 77.2%, sensitivity 90% specificity 70%; and the doubtable value interval was 6.23E-03-2.29E-02.The serum IP-10 levels in breast carcinoma patients were down-regulated 57.0% than in normal controls (p=0.000). The serum IP-10 level was uncorrelated with ER/PR status, Her-2 status, lymph nodes status, nucleus grade and clinical stage (p >0.05).The optimal operating point of serum IP-10 level was 59.90 pg/ml, which positive predictive value 87.2%, sensitivity 77.3%, specificity 81.5%, and the doubtable value interval was.52.96～68.00pg/ml.CONCLUSION (1) CXCL10 mRNA expression in breast carcinoma was up-regulated than in normal tissues and benign tumors, implicating that CXCL10 mRNA expression was related with tumorigenesis of breast carcinoma, and CXCL10 may be considered as molecular marker of differential diagnosis in breast carcinoma. (2) CXCL10 mRNA expression in primary breast carcinoma and cell lines was related with ER,PR and Her-2 status, suggested that interaction may exist between CXCL10 and ER, CXCL10 and Her-2, overexpression of CXCL10 was related with poor prognosis. (3) The serum IP-10 levels in breast carcinoma patients were significantly down-regulated than in normal controls, and the change tendency of which had a positive correlation with malignancy degree. It had been suggested that the serum IP-10 levels may assist breast carcinoma screening, and differential diagnosis between breast benign and malignant tumor.