Study On Breast Cancer Detection Based On Serum Protein Surface-enhanced Raman Spectroscopy

Breast cancer affects women’s health.At present,the preoperative screening and postoperative evaluation of breast cancer are mainly imaging detection combined with histopathological analysis,but these methods have unavoidable subjective assumptions and poor results for tiny tumors.At the same time,it causes varying degrees of harm to the patient’s mind and body.In this paper,human serum was used as the research object,and the surface enhanced Raman spectroscopy technology with high sensitivity and single-molecule detection ability was used as the research method.Human serum as the research object,the surface enhanced Raman spectroscopy technology used(SERS)as a research method combined with multivariate statistical algorithms,by cellulose acetate membrane extraction of serum protein compared with conventional breast cancer patients serum,grade of ammonium sulfate precipitation of serum protein and tumor markers carcinoembryonic antigen(CEA)used in the SERS detection analysis.Multivariate statistical analysis for statistically analyze the results found that it could promote breast cancer screening,evaluation,low-cost,non-destructive,fast and accurate diagnostic methods.The following is the main contents of our research works.1.Protein purification using cellulose acetate membrane was combined with SERS technology for the detection,diagnosis and postoperative evaluation of breast cancer patients.Firstly,Cellulose acetate membrane was used to extract serum proteins from 30 healthy volunteers and 30 Breast cancer for before and after operation,and the serum protein SERS spectrum was obtained.Combined with the PCA-LDA statistical analysis to distinguish the serum protein SERS spectra of preoperative,postoperative of Breast cancer and normal groups,the diagnostic sensitivity reached 96.7%,53.3%,100%,and the specificity reached 96.7%,46.7%,96.7%,respectively.The serum samples are divided into three groups for SERS measurement.One group was 30 healthy volunteers and the other was 30 preoperative Breast cancer serums.The thirdly group was 30 cases of Breast cancer postoperative serum(the preoperative and postoperative serum was taken from the same Breast cancer patient).To better analyze the data,the SERS data were de-fluorescence background and normalized.In addition,the software SPSS was used to reduce dimensionality,principal component analysis(PCA)combined with linear discriminant analysis(LDA)was used to distinguish among preoperative,postoperative and normal Breast cancer groups.The diagnostic sensitivity and specificity reached 80%(24/30)and,83.3%(25/30)and 86.7%(26/30),90%(27/30)and 93.3%(28/30)respectively.Through comparative discussion,the following conclusions were drawn:serum protein can well realize the postoperative evaluation of BC,and the effect was better than that of serum samples,while serum has little reference value in the postoperative evaluation of BC.2.The method of ammonium sulfate fractionated precipitation serum protein was combined with SERS technology to detect and analyze breast cancer.For the first time,ammonium sulfate grading precipitation of serum protein combined with SERS spectrum detection method was used to diagnose and screen breast cancer.60 cases of preoperative,postoperative breast cancer patients and healthy volunteers serum protein were tested by SERS technique.PCA and LDA algorithm were used for SERS spectra statistical analysis.The results show that different precipitation levels(30%,50%,70%)serum protein with preoperative and postoperative of breast cancer,preoperative cancer group and normal group,postoperative cancer group and normal group the discriminant accuracy respectively: 75%(45/60),90%(54/60),96.7%(58/60)(30% precipitation serum protein);85%(51/60),100%(60/60),88.3%(53/60)(50% precipitated serum proteinome);88.3%(53/60),95%(57/60),86.6%(52/60)(70% precipitated serum proteome).Compared with conventional serum SERS spectrum detection,the total serum protein SERS spectrum detection effect was improved and breast cancer markers were found to be most likely to exist in serum globulin or albumin.3.Carcinoembryonic antigen(CEA)as a tumor marker was combined with SERS technology for Breast cancer label detection research.Using 4-mercaptobenzoic acid(4-MBA)as the probe molecule,the 4-MBA and the aptamer of CEA were connected to the gold nanospheres,and CEA was joined to the silicon plate with Au NPs(with antibody of CEA)to form a sandwich structure.,To achieve the purpose of Breast cancer diagnosis,indirect detection of carcinoembryonic antigen were performed by SERS technoloy.The results of 20 samples showed that the CEA with a concentration of10ng/ml as the dividing line had good diagnostic performance and the detection limit could reach 0.08ng/ml.The test of 20 samples showed that the CEA at a concentration of10ng/ml was used as the dividing line,which has good diagnostic performance.The results of our exploratory research in this paper show that: serum proteins extracted by cellulose acetate membrane and serum proteins precipitated by ammonium sulfate were combined with PCA-LDA statistical analysis method and CEA sandwich structure SERS sensor have great potential in preoperative detection and postoperative evaluation for breast cancer patients with low cost,non-invasive,rapid and accurate direction.