The Potencial Clinical Significance Of Serum Marker VN In The Diagnosis Of Early Breast Cancer

Background: The incidence of breast cancer is the first in female malignant tumors. There are over one million new cases of breast cancer and about 410,000 people dying of breast disease each year.So the early diagnosis and treatment play a vital role in reducing the mortality of the breast cancer patients,improving the patients ’ quality of life and extending the lifetime.However, it has difficulty in the early diagnosis of the disease due to the complexity and damage of the commonly used methods.But serum biomarkers are more appealing due to their simplicity, noninvasion, and continuous observation of objective. However, most of the biomarkers currently used in clinical settings including cancer antigen 15-3(CA15-3) and carcinoembryonic antigen(C EA) are frequently elevated in patients with metastatic disease and lack sensitivity in detecting primary breast cancer at an early stage, none of them is useful for early diagnosis of BC. Therefore, it is very urgent to find serum tumor-specific markers with high sensitivity and specificity for early effectively diagnose of Breast cancer.Objective: This study aims to explore the the clinical significance of serum marker VN in the diagnosis of early breast cancer by ELISA and to further explore t he value of the single and combined detection of C EA, CA15-3, VN in the early breast cancer diagnosis. Method: The serum concentrations of VN was detected in all samples by ELISA method,(including 93 patients with breast cancer, 30 patients with breast benign lesions, 9 patients with precancerous lesions, 30 normal female), Combined with the clinical value of serum CA15-3 and CEA, and some clinical and pathological parameters were collected. SPSS17.0 statistic software was applied to analyze these data. P values less than 0.05 were considered statistically significant for all statistical analyses.Results: 1 Serum VN, CA- 153, CEA expression in breast cancer and breast benign lesions, precancerous lesions and normal control group.serum VN levels were higher in the stage 0-Ⅰ(310.98±36.78μg/ml)breast cancer patients than the female normal control(NF)(277.23±45.86μg/ml)、 benign breast lesion(292.57±35.28μg/ml)、precancerous lesion patients(282.05±31.25μg/ml) and cancer patients of stageⅡ(274.67±38.12μg/ml)、stageⅢ-Ⅳ(270.78±48.08μg/ml)(P< 0.05), but no significant difference has been found among the other groups(P > 0.05). The mean value of serum CA15-3 concentrations in Stage 0-I breast cancer patients(12.45±5.68U/ml) was significantly higher than in normal control(8.49±2.56U/ml) and benign lesion groups(8.51±3.80 U/ml),so were the stageⅡ(15.95±5.61U/ml) and stageⅢ-Ⅳ(18.83±8.56U/ml)(P< 0.05). Similarly, the mean value of serum CEA concentration in Stages 0-I breast cancer patients(5.55±5.44ng/ml) was significantly higher than in the normal control(1.09±0.43ng/ml) and benign lesion groups(1.11±0.83ng/ml),so were the stage stageⅡ(13.68±9.19ng/ml) and stageⅢ-Ⅳ(18.27±11.21ng/ml)(P< 0.05).And the mean value of serum C EA concentration in StagesⅡand stageⅢ-Ⅳ breast cancer patients were significantly higher than precancerous lesion patients.However, both serum CEA and CA15-3 levels in Stage 0-I showed no significant difference compared to Stage II, Stage III-IV breast cancer patients and precancerous lesion patients(P>0.05 in all cases) 2 Association between serum VN,CA-153,CEA levels and clinicopathological parameters of breast cance r patients respectively. serum VN levels were not associated with Age, Menstrual status, Histological grade, estrogen receptor(ER)expression, progesterone receptor(PR) expression, HER2 overexpression and K i67 expression(P >0.05). But the serum VN concentrations were more frequently associated with Tumor Size, Lymph node status and C linical stage(P <0.05). A general trend was observed with decreased VN levels corresponding to increased tumor Size(P =0.0175) and C linical stage(P =0.0004). And the serum VN in Lymph node negative group was higher than the positive group(P =0.0024). As to the C EA and CA15-3, serum CA15-3 and CEA were significantly increased in patients with tumor size >2cm, compared to patients with tumor size< 2cm. Serum C EA and C A15-3 were significantly increased in patients with C linicalstage. Significant differences were found in the levels of C A15-3 and C EA between lymph nodal negative and positive patients(P < 0.05). 3 Correlations and diagnostic values among the three markers in 0-Ⅰstage of breast cancer patients. There is no significant correlation among the three serum markers in 0-Ⅰstage of breast cancer patients(P>0.05). In order to quantify the diagnostic value of the three markers, ROC curve analysis was done. All three markers have AUC significantly better than 0.5, with VN having the best performance(AUC=0.73, 95% CI [0.37, 0.67]). Combined analysis of AUC for the three markers VN, CEA and CA15-3 resulted in an increase of areas(AUC=0.83, 95% CI [0.74, 0.92]). Conclusion: Taken together, this data indicates that VN can be used as a breast cancer marker capable of discriminating stage 0-Ⅰbreast cancer patients from the female control at higher sensitivity than CEA and CA15-3. Combining VN, CEA and CA15-3 increase the probability with superior sensitivity for early breast cancer diagnosis.