Evaluation Of The Value Of Preoperative Sialic Acid Levels In Diagnosis And Localization Of Urothelial Tumor

Background:Urothelial carcinoma(UC)is the ninth most common cancer and is the thirteenth most common cause of death due to cancer,accounting for approximately 430,000 new cases and 165,000 mortalities globally.In China,there are 80,500 incident cases and 32,900 mortalities caused by UC each year.UC is the most frequent type of cancer of the bladder(BUC)and upper urinary tract,while the morbidity and mortality of UC have gradually increased over recent years.Therefore,early detection and diagnose have an important significance to the prognosis and quality of life of patients with UC.Cytological experiments and biopsies under a ureteroscope and a bladder scope are currently the two main means of UC early detection and diagnosis.However,use of the ureteroscope and bladder scope not only is invasive but also has a high rate of missed diagnosis,especially for UC in situ and upper tract urothelial carcinoma(UTUC).Therefore,the search for a specific,highly sensitive marker,that can predict the biological behavior of UC,as an index for predicting tumor progression and metastasis,in order to guide clinical diagnosis and therapy is particularly important.Sialic acid(SA)is a monosaccharide with a nine-carbon backbone that occupies the terminal position on macromolecules and cell membranes.SA is involved in autoimmune diseases,microbial invasion,virulence pathogenesis and tumor growth.Malignant cells often have an increased concentration of SA on the surface and secrete SA to increase the concentration in blood.In previous studies,it was found that the lipid-bound subfraction of SA concentration was of limited value for detecting early stages of genitourinary malignancies.However,small sample sizes,no further analyses of multiple factors,no assessment of localization values and no validated cut-off values existed in these studies.Therefore,the present study aimed to assess SA levels in patients with UC to determine the pathogenesis and development of UC.Objection:1.To evaluate the value of S A in diagnosis of UTUC and BUC;2.To evaluate the value of SA in localization of UC.Materials and methods:1.Patients.From July 2014 to April 2018,the clinical data of 591 patients with urothelial carcinoma who underwent surgical treatment in the Department of Urology,Qilu Hospital of Shandong University,were retrospectively analyzed.Among 591 UC patients,406 patients were diagnosed with bladder tumors,99 with ureteral tumors and 86 with renal pelvic tumors.2.Date collection.Clinical data including patient age at the time of diagnosis,sex,smoking history,routine blood examination results(white blood cell count,platelet count,plasma fibrinogen level,etc.),and tumor characteristics were obtained from the electronic patient records at our institution.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 records.4.Statistical analysis.The Kolmogorov-Smirnov test was adopted to assess whether the level of SA conformed to a normal distribution,and the values were presented as the mean± standard deviation(SD).Student’s t-test and one-way ANOVA were used for normally distributed data;if the data distribution was not normal,the Mann-Whitney U-test and Kruskal-Wallis H-test were employed for the nonparametric analysis.Data were analyzed and processed using the Statistical Package for Social Sciences version 22.0(SPSS Inc.,Chicago,IL,USA).P values<0.05 in two-tailed tests were considered statistically significant.Results:1.Clinicopathological characteristics ofpatientsThe serum levels of SA in advanced-stage patients were significantly higher than those in early-stage patients(Fig 2).However,there was no statistically significant difference in SA levels among UC,PUNLMP and papilloma cases(BUC:p=0.757,UTUC:p=0.647,Fig 2).2.The role of SA level in the localization diagnosis of UCOf all patients,406(68.70%)had bladder tumors,99(16.75%)had ureteral tumors,and 86(14.55%)had renal pelvic tumors.Our study found that the serum SA level in the renal pelvic tumor and ureteral tumor groups was significantly higher than that in patients with bladder tumors(p<0.05,Fig 2D and Table 2).3.Correlation analysesLinear correlation analyses were conducted to further explore correlations between SA levels and WBC,PLT,LDH,AKP,and PFL in UC patients.We found that there was a significant positive relationship between serum SA levels and WBC(r=0.300,p<0.05,Fig 3A),PLT(r=0.416,p<0.05,Fig 3B),AKP(r=0.336,p<0.05,Fig 3C),LDH(r=0.250,p<0.05,Fig 3D),and PFL(r=0.378,p<0.05,Fig 3E).4.The value of serum SA level in accurate location and qualitative diagnosisfor UC patients.The optimal threshold values for preoperative SA levels were>52.27 mg/dL,>49.40 mg/dL(UC vs.papilloma and PUNLMP,BUC and UTUC),>61.60 mg/dL,>48.35 mg/dL(high-grade UC vs.low-grade UC,BUC and UTUC),>54.35 mg/dL,>58.35 mg/dL(MIUC vs.NMIUC,BUC and UTUC),and 60.31 mg/dL(UTUC vs.BUC).Remarkably,there was no clinical value of SA levels in differential diagnosis of UC and papilloma and PUNLMP(BUC:p=0.791;UTUC:p=0.385).Univariable and multivariable logistic regression analyses were conducted to further explore the clinical application value of serum SA levels for predicting the prognosis and orientation of urothelial tumors.We found that SA level>61.60 mg/dL,SA level>48.35 mg/dL and SA level>60.31 mg/dL were independent risk factors for high-grade BUC(HR=1.941,p<0.05;Table 4),high-grade UTUC(HR=3.820,p<0.05;Table 4),and UTUC(HR=2.047,p<0.05;Table 4),respectively.Conclusions:In conclusion,we believe that SA can be a useful biomarker for the evaluation of the malignant degree of UC and the localization of urothelial tumors.However,further studies are needed to determine whether serum SA levels have applicable clinical value as a single biomarker or as an auxiliary test to traditional approaches in the detection and localization of urothelial tumors.