Screening For Tumor At Early Stage And Detection Of Cancer Based On Serum P53Antibodies

Cancer has been the most dangerous threat to human health and the top case of death incity and countryside of China. In China, approximately2.6million people were diagnosedwith cancer each year, and about1.8million persons died. At present,80%cancer patientswere in terminal as they were diagnosed, losing the best treatment opportunity. The reasonsfor this phenomenon are diverse, and one of the most important reasons is that there is still noreliable way to detect and prevent cancer in the early time.Thyroid cancer is the most common malignant tumor of endocrine system, and the mostfrequent type of thyroid malignancy is papillary thyroid carcinoma (PTC), which accounts forapproximately80%to90%of all thyroid malignancies. However, the preoperative diagnosisresults of some patients are indeterminate, causing misdiagnosis in our clinical practice. Thereis no effective serum marker for PTC so far. Therefore, it is of high necessity to identify theadditional diagnostic and prognostic markers that facilitate the improved and personalizedmanagement of patients with PTC.Serum p53antibodies were a broad-spectrum of tumor marker, which were found inpatients with various types of cancer and persons at high risk of cancer. To our knowledge nodata is available in the literature on the prevalence of p53antibodies and their usefulness as atumor marker for check-up crowd and PTC. Whether serum p53antibodies could be used asan early tumor marker for check-up crowd and a relevant diagnostic and prognostic markerfor PTC need further research. The common method used in the detection of serum p53antibodies is enzyme-linked immunosorbent assay (ELISA). However, the detection rate oftraditional ELISA method is low, and it was time-consuming and laborious to gain high purityrecombinant protein. In this study, we choose check-up crowd and patients with PTC or breastcancer as the subject to explore the problems mentioned above.To determine whether serum p53antibodies could be used as an early tumor marker forcheck-up crowd, we detected1162and3168participants who received routine physicalexamination using ELISA method at different years, and correspondingly,26positiveindividuals and96positive persons were detected by ELISA method. Results from follow-upand multi-tumor markers revealed that serum p53antibodies correlate with multi-tumormarkers, and some positive persons developed cancer gradually. Therefore, serum p53antibodies could be used as an early tumor marker for check-up crowd.To determine whether p53antibodies could be a relevant marker for PTC, we preparedrecombinant P53protein and two types of filamentous bacteriophages for the detection ofserum p53antibodies.117cases with thyroid adenoma and187PTC patients were enrolled inthis study. Compared with P53protein and SS-phage, phage-SP showed a higher sensitivityand specificity in the detection of serum p53antibodies from patients with PTC, and therewas a marked difference in general between the PTC group and benign control group forserum p53antibodies. Further analysis revealed that p53antibodies were positively associated with clinical stage, node metastasis and P53protein accumulation. These results indicate thatserum p53antibodies could be a useful marker for PTC.Firstly, we displayed one epitope belonging to the immunodominant region of P53protein on the PIII or PVIII protein to compare the detection efficiency between the twodisplay systems. Then, we prepared an novel dual display phage displaying two differentpeptides of P53protein on the PIII and PVIII protein to increase the detection efficiency.Results revealed that both PIII and PVIII display system could be used for the detection ofserum p53antibodies, and almost all the positive cases detected by two display systems wereidentical. Compared with P53protein and phage displaying one peptide, the dual displayphage showed a higher a higher sensitivity and specificity. P53protein and the dual displayphage were complementary in the detection of serum p53antibodies, and a combination ofP53protein and the dual display phage could improve the detection rate of p53antibodiesthan using each of the individual antigen. This inexpensive and sensitive bifunctional phagepaves the way to the wide range usage of antibody biomarkers and this bifunctional phage hasthe potential to develop into a new type of diagnosis reagent.