A Study On Prostate Cancer Screening Based On SERS Detection Of Serum Proteins

Prostate cancer,which has the highest incidence in the United States and Western Europe,is the most common solid organ malignancy affecting men,and early detection and screening will greatly improve survival rates and reduce complications for prostate cancer patients.Although the measurement of serum prostate-specific antigen（PSA）levels is the current gold standard for prostate cancer diagnosis,the low sensitivity and poor predictive score of PSA based screening results in overdiagnosis and unnecessary biopsies in 22%to 43%of patients.It also delays the detection of metastatic disease,resulting in many prostate cancer patients being diagnosed at advanced stages,resulting in poor survival.Serum markers play a key role in early diagnosis,prognosis and treatment response monitoring.With the generation of inflammation,serum protein levels will also change accordingly.Several studies have shown that serum protein detection has considerable significance in biomedical engineering,as it can be used as a highly sensitive and reliable cancer diagnostic indicator.The purpose of this research is to use different technologies to extract proteins related to the progression and aggressiveness of prostate cancer and to develop a rapid,non-invasive and sensitive detection method for early prostate cancer by combining with the SERS technology with molecular fingerprinting recognition ability.Main research contents include:1.To explore the feasibility of SERS in the diagnosis of prostate cancer,two data processing methods,PCA-LDA and PLS-SVM,were used to analyze and compare the SERS data of 30 cases of prostate cancer and 30 normal human serum samples obtained,and further applied in the detection of early prostate cancer.This work indicated that SERS combined with PLS-SVM algorithm had great potential in cancer screening analysis,which provided a reliable method for data analysis in the following experiments.2.SERS detection of total protein in serum of prostate cancer based on cellulose acetate membrane（CA）.Serum is rich in protein,which can change under inflammatory conditions.In this chapter,CA membrane was used to extract total serum protein from 30patients with prostate cancer and 30 healthy volunteers,and the extracted protein was mixed with silver nanoparticles for SERS detection,and the SERS data was analyzed by combining PLS-SVM algorithm.This exploratory work suggests that the label free SERS analysis technique combined with CA membrane purification of serum total proteins has potential in prostate cancer diagnosis.3.SERS detection of serum albumin of prostate cancer based on HAp spheres.Serum albumin level is closely related to the survival of prostate cancer patients,and is also a good indicator of tumor prognosis.In this study,a novel albumin extraction and analysis method was proposed for the detection of prostate cancer.HAp specific adsorption capability was utilized to target albumin in serum.Serum albumin extracted by HAp spheres was combined with SERS and PLS-SVM algorithm for the early detection of prostate cancer.The results showed that albumin has great potential in the early diagnosis of prostate cancer.4.SERS detection of serum albumin of prostate cancer based on HAp flowers.In this paper,HAp flowers and HAp spheres with different nanostructures were synthesized by hydrothermal method,and the targeted binding and extraction ability of these two HAp particles on serum albumin were compared.The adsorption and release of serum albumin by HAp flower can be completed within 1 h,which is much faster than the 24 h purification required by HAp spheres.Serum albumin was extracted by HAp flower adsorption and mixed with Ag NPs for SERS spectrum analysis.The SERS spectrum analysis of serum albumin obtained by PLS-SVM algorithm showed that the accuracy of diagnosis in early stage（T1-T2 stage）prostate cancer could reach 98.2143%.The results show that the PLS-SVM model provides superior performance in the classification of prostate cancer diagnosis.The combination of HAp adsorbed release albumin and SERS has the advantages of simple,rapid,accurate,and cheap,which is expected to be a powerful tool for prostate cancer diagnosis and precision medicine.5.SERS detection of serum albumin in prostate cancer based on flowery HAp/Ag substrate.In this chapter,we develop a novel method to obtain stable Raman signals of serum albumin using HAp and Ag nanoparticles composites.Silver doped hydroxyapatite nanocomposite（HAp/Ag）can inhibit the oxidation of silver nanoparticles,making SERS substrate not only solve the problem of"coffee ring effect"of silver colloid,but also have good stability and reproducibility.HAp/Ag substrate was used for quantitative analysis of crystal violet,and the linear relationship between 10^-2and 10^-5M was good.Subsequently,HAp/Ag nanocomposite SERS substrate was used to detect serum albumin extracted by HAp flower.The results showed that the method proposed in this chapter was helpful to establish a sensitive and non-invasive method for prostate cancer screening based on SERS detection of serum albumin.Based on the urgent need for early screening of prostate cancer,this paper designed experimental schemes for the extraction of serum protein and serum albumin respectively and combined SERS technology and PLS-SVM algorithm to detect prostate cancer and normal human samples.This study not only proposed an effective method for extracting proteins from serum,improving the accuracy of early detection of prostate cancer,but also expected to expand its application in the early screening of other cancers,which has great potential in clinical application.