Study Of Circulating Autoantibodies To Tumor-associated Antigens In Breast Carcioma

ObjectiveBreast cancer is a serious impact on women’s physical and mental health and evenlife-threatening, one of the most common malignant tumor incidence is behind to lungcancer. Due to the lack of specificity of clinical diagnostic markers, most patients havebeen found in the late,so that lose the chance of radical surgery. Therefore, earlydiscovery, early diagnosis, early treatment for breast cancer is still the top priority. Inrecent years, autoantibody as markers in early diagnosis of breast cancer has beenwidely recognized, already in Europe and North America for commercial applications.This study used a new ELISA method to detect breast cancer with immunomodulatorymolecules in peripheral blood and tumor related antigen antibody levels itself,immunomodulatory molecules and the correlation of tumor related antigen antibodylevels itself, immunomodulatory molecules and tumor related antibodies in thepathogenesis of tumor effect and influence each other, looking for early diagnosis oftumor markers.MethodChoose four molecules in this study, including an immune regulating factor:transcription growth factor beta1(Transforming growth factor beta1, TGF–β1); Threetumor related antigen: multiple tumor suppressor1(multiple tumor suppressor1, P16),tumor suppressor P53(tumor suppressor P53, TP53), proto-oncogenes c-myc(cancer-myc, c-myc). Using bioinformatics database and comprehensive analysis ofprotein structure and nature of software design of four molecular peptide antigenfragments, using the method of optimization of ELISA detection of breast cancerpatients with peripheral blood four corresponding peptide antigen antibody levels, andselect the physical examination for a control, to>200cases of mixed blood of healthyphysical examination for the quality control samples, using SPSS20.0software for X2test and ROC curve analysis.Result1. The immune regulatory molecules： (1)the peptides:TGF-beta1:H-LYQKYSNNSWRYLSNRLLILSKLRLASPPSQ-OH(2) antibody testing: breast cancer patients with peripheral blood anti-TGF–β1levelshigher than the healthy group (P>0.05), but not diagnostic significance. Breast cancerpatients with anti-TGF–β1IgGROC area under the curve is0.516, sensitivity of11.5%,specificity of90.4%, the results showed that the anti-TGF–β1IgG the diagnosis of earlybreast cancer have a good negative prediction efficiency, but no positive predictivevalue.2. The tumor related molecules:(1) The peptides：here are the sequence of the three immune regulatory molecules：P16:H-NSYGRLVVLHRAGARLDVRDAWGRLPVDLa-OH;TP53:H-LIRVEGNLRVEYPGTRVRAMAIYKQSQHMTE-OH;C-myc:H-RVKLDSVRVLRQISNNRKCFELLPTPPLSPS-OH(2)The levels of autoantibodies: anti-P16IgG level of breast cancer was obviouslyhigher than that of healthy group (P=0.001), the positive rate of the patients was22.5%,higher than in healthy group (P <0.05), with the increase of clinical stage, positive rategradually decreases. The results showed that the anti-P16IgG the diagnosis of earlybreast cancer have a certain accuracy. Breast cancer patients Ⅰ-Ⅲ period rate of slowdown, Ⅳ period rise again. Results show that the obvious anti-P16IgG levels in breastcancer diagnosis meaning, anti-P16IgG levels rise, especially in early stage (Ⅰ) IgGlevels rise, are risk factors for breast cancer (P <0.05). Breast cancer patients with anti-P16IgG area under the ROC curve is0.730, the sensitivity was33.3%, specificity of90.0%. Shows that anti-P16IgG meaningful to the diagnosis of breast cancer patients.Breast cancer patients with peripheral blood ati-TP53IgG level higher than the healthygroup (P <0.05), the statistical differences (P <0.05); Ⅰ period, Ⅱ period alsostatistically significant, breast cancer patients with ati-TP53IgGIgGROC area underthe curve is0.616, specificity of90.4%, the sensitivity was10.5%, the missed diagnosisand misdiagnosis rate slightly on the high side, slightly lower sensitivity, so itsdiagnostic value is not high. Breast cancer resistant to C-myc autoantibody levels aresignificantly higher than healthy controls (P <0.05), statistically significant, the clinicalstaging are also statistically significant, but the degree of sensitivity and specific slightlylow, AUC is0.686, it has certain reference value.Conclusion(1) In the peripheral blood of patients with breast cancer, anti-P16IgG may be a new diagnostic markers. Changes in the level of anti-P16IgG has certain correlationwith breast cancer, we need further investigation to verify the potential value of P16inthe future.(2) Circulating anti-C-mycIgG may also be a novel diagnostic marker for breastcancer.(3) Circulating anti-P16IgG showed a weak association with both NSCLC andESCC. Further investigation is needed to confirm whether anti-p16IgG can serve as apotential marker for thoracic cancers.(3) Circulating autoantibodies for TGF-β1and TP53did not show a significantchange in patients with BC, although initial work from a number of studies have theirincrease in circulating levels in lung cancer. Possibly, further mapping of HLA restrictedantigens is needed in future study.(4) The present work was undertaken to develop an in-house ELISA test with thestronger specificity. This is a novel method and may a very useful for detection ofcirculating antibodies as biomarkers for cancer.