Serum Proteomic Patterns For Prostate Cancer Revealed By SELDI Mass Spectrometry

Objective:SELDI-TOF mass spectrometry was used to investigate protein expression in sera of patients with prostate cancer and benign prostate hyperplasia compared to healthy men.To establish a serum protein pattern model for screening prostate cancer,and used it to identify proteomic patterns in serum that distinguish neoplastic from non-neoplastic disease within the prostate cancer.Methods:Training group:prostate cancer patients 22 samples(confirmed by pathology),benign prostate hyperplasia patients 26 samples(confirmed by pathology), healthy men 31 samples.Independent group:prostate cancer 12 samples,noncancer 18 samples.SELDI-TOF mass spectrometry was used to investigate protein expression in sera of patients with prostate cancer and benign prostate hyperplasia compared to healthy men.A preliminary "training" set of spectra derived from analysis of serum from 22 patients with prostate cancer and 26 patients with benign prostate hyperplasia and 31 healthy men were analyzed by an iterative searching algorithm that identified a proteomic pattern that completely discriminated cancer from noncancer.The discovered pattern was then used to classify an independent set of 48 masked serum samples:12 from prostate cancer and 36 from noncancer.Results:1.A comparison of protein mass spectra obtained from the sera of the prostate cancer group and the healthy men group revealed 86 protein peaks.There were statistical differences between 4 protein peaks located at 11665 Da,2958 Da, 7978 Da,3092Da(P＜0.0001);The intensity of protein peaks at 7978Da in the sera from patients with prostate cancer was clearly higher than that of the healthy men. Bi-peak or tri-peaks at 7978 Da were also observed in the sera from patients with prostate cancer.Using the above profiles,21 of 22 patients diagnosed pathologically with prostate cancer were correctly identified by SELDI.26 of 31 healthy men were correctly identified as normal.The sensitivity of neoplastic identification was 95.45%(21/22)for patients whereas the specificity of control verification was 83.871%(26/31).Using these criteria,prostate cancer was correctly identified in 11 out of 12 samples,and 16 out of 18 of the healthy men were identified.The biomarkers therefore had an accuracy of 91.67%(11/12)and 88.89%(16/18)for the identification of prostate cancer and of the healthy men respectively.2.A comparison of protein mass spectra obtained from the sera of the prostate cancer group and benign prostate hyperplasia group revealed 83 protein peaks.There were statistical differences between 3 protein peaks located at 3191Da,3271Da, 1127Da(P＜0.01).The intensity of protein peaks at 3191Da,3271Da in the sera from patients with prostate cancer was clearly higher than that of benign prostate hyperplasia.Further the protein peak at 1127Da in the sera from patients with prostate cancer was down-regulated compared to benign prostate hyperplasia.Using the above profiles,21 of 22 patients diagnosed pathologically with prostate cancer were correctly identified by SELDI.And 25 of 26 benign prostate hyperplasia were correctly identified by SELDI.The sensitivity of neoplastic identification was 95.45%(21/22)for patients whereas the specificity of control verification was 96.15% (25/26).Using these criteria,prostate cancer was correctly identified in 11 out of 12 samples,and 15 out of 18 benign prostate hyperplasia were identified.The biomarkers therefore had an accuracy of 91.67%(11/12)and 83.33%(15/18)for the identification of prostate cancer and benign prostate hyperplasia respectively.Conclusions:Use the SELDI-TOF mass spectrometry to establish a serum protein pattern model for screening prostate cancer,and identify proteomic patterns in serum that distinguish prostate cancer from healthy men.The importance of our studies has been to demonstrate the usefulness of SELDI in the discovery of potential tumor markers in serum samples.The comparison of protein expression profiles from serum appears to provide an effective approach to identifying unique biomarkers for prostate cancer and benign prostate hyperplasia.Larger scale studies appear warranted to confirm the ability of SELDI as a proteomic screen in the clinical setting.