Elevated Serum Sialic Acid Levels Predict Prostate Cancer As Well As Bone Metastases

Background:Prostate cancer(PCa)is a malignant tumor that originates from the man reproductive system,which is becoming a great detriment to male health.Although the incidence of PCa in Asian was lower than that in United States and Europe,the morbidity and mortality of PCa in China is increasing rapidly with the changing of lifestyle.The traditional prostate cancer marker,prostate-specific antigen(PSA),also has some problems such as high costs,long waiting time,and low specificity and sensitivity.Furthermore,PCa was prone to be bone metastases,and a considerable proportion of the patients had been advanced stage once diagnosed.However,there is no ideal screening and predictive indicators for bone metastases at present.Emission computerized tomography(ECT)is most commonly used in assessment of bone metastases in PCa patients and it is regarded as one of the most effective detection methods for bone metastases.However,the examination was expensive and had certain radioactivity.We found SA level was seemly elevated in PCa patients,but the research about the phenomenon was few.Therefore,we investigated the SA level in patients with prostate neoplasia in order to verify it's values in the diagnosis of BPH.PCa,as well as bone metastases in Chinese population,and we further give the optimal cut-off SA level separately.Objection:1.To evaluate the value of SA in diagnosis of prostate cancer(PCa);2.To evaluate the value of SA in diagnosis of bone metastases in PCa patients.Materials and methods:1.Patients.Based on inclusion and exclusion criteria,a retrospective collection of medical records was performed for 540 patients who were newly diagnosed as PCa or BPH and treated at the Department of Urology,Qilu Hospital of Shandong University.between December 2014 and April 2018.Among 540 patients,408 patients were diagnosed as PCa,and 132 patients were diagnosed as BPH.The diagnosis of all patients had been confirmed by the biopsy or postoperative pathology.2.Date collection.Clinical data including patients' age at the time of diagnosis,prostate specific antigen(PSA),pathological characteristics(including pathological grade and stage),prostate volume(PV)and ECT and other essential information were retrieved from the electronic patient records at Qilu Hospital of Shandong University.3.SA measurement.SA level is one of the important components of serum biochemistry,which was routinely tested before surgery.We obtained the preoperative level of SA from patient's medical records4.Statistical analysis.Student's t-test was used for normal distribution data,if not,the Mann-Whitney U-test or Kruskal-Wallis H-test was employed.The receiver operative characteristic(ROC)was adopted to determine the optimal threshold of SA level for different diagnosis.Univariate and multivariate regression models were constructed to further evaluate the value of SA levels in differentiating pathological outcomes.All tests were two-tailed and "p" less than 0.05 was regarded as statistically significant.All data were analyzed using the Statistical Package for Social Science version 22.0(SPSS Inc,Chicago,IL,USA)and GraphPad Prim 6 software(GraphPad Software Inc,San Diego,CA,USA)Results:1.Baseline clinical characteristics ofstudypopulation.All the patients included in the present study consecutively presented at the Department of Urology,Qilu Hospital of Shandong University.After eliminating unqualified patients according to the exclusion criteria,540 patients were eligible for inclusion in the finally study.Based on pathologic findings,408 were PCa and 132 were BPH.The mean level of SA in the PCa cohort was 56.75±11.47 mg/dL,which was significantly higher than that in the BPH patients(54.05±9.00 mg/dL)(p=0.013)(Table 1,Fig.1 A)2.Associations between SA levels and clinicopathological characteristics of PCa patients.The associations between SA levels and clinical characteristics of 408 PCa patients were further evaluated.It was significant that pretreatment SA levels were associated with LDH,AKP,FIB,and PSA(all p<0.001)(Table 2,Fig.2A,B,C,D).The mean level of SA in patients with bone metastases was significantly higher than that with suspicious bone metastases or without bone metastases(bone metastases:69.97± 15.14 mg/dL;suspicious bone metastases:59.89 ±12.24 mg/dL;without bone metastases:54.58 ± 9.74 mg/dL,respectively.p<0.001)(Table 2,Fig 1B).When considering pathological grade of PCa patients on the basis of Gleason score(GS),SA levels in men with high grade cancer(GS>7)were elevated compared to the low grade(GS?7)(58.34±13.05 mg/dL vs 55.11±9.43 mg/dL;p=0.024)(Table 2;Fig.2E).3.Prognostic value of preoperative SA levels in predicting PCa and bone metastases The ROC curve for pretreatment SA levels was plotted to assess its predictive value for PCa.The optimal threshold values for SA levels was 52.35 mg/dL(PCa vs BPH).The area under the ROC(AUC)was 0.57(95%CI 0.52 to 0.63),and the sensitivity.specificity,positive predictive values(PPV),negative predictive values(NPV)were 60.0%,58.6%,81.7%,and 32.1%respectively(Fig.4A).According to the ROC curve drawn by the SA levels of patients with bone metastases or without bone metastases,we found that AUC was 0.82(95%Cl 0.73 to 0.90),and the optimal threshold value was 59.00 mg/dL.The sensitivity,specificity.PPV,and NPV were 82.9%,78.7%,61.8%,93.5%respectively(Fig.4B).Logistic regression analysis was constructed to further analyze the clinical impact of pretreatment SA levels in the diagnosis of PCa and bone metastases.In the univariate and multivariate analysis,the results indicted elevated SA levels were statistically significant for prediction of PCa and bone metastases(p<0.001,Table 3 and Table 4)Conclusions:The present study demonstrated that preoperative SA levels in PCa patients were significantly higher than BPH patients,and elevated SA levels were closely associated with bone metastases.This study suggested that SA levels may be a promising biomarker and a reliable predictor for PCa and bone metastases.