| BackgroundBy 2020 the estimated incidence of genitourinary(GU)cancers(prostate,bladder,and kidney)will be over 2 million worldwide and responsible for approximately 800000 deaths.Bladder cancer is the second most common malignancy of the urinary tract and one of the most frequent malignancies world-wide.The majority of bladder cancers are transitional cell carcinomas,which account for more than 90%of all cases,while squamous cell carcinoma and adenocarcinoma are less prevalent.Leiomyomas of the bladder constitute<0.5%of all bladder tumors.According to the World Health Organization/International Society of Urological Pathology(WHO/ISUP)classification,bladder urothelial tumors are categorized into three subtypes:papilloma,papillary urothelial neoplasm of low malignant potential(PUNLMP),and carcinoma(bladder urothelial carcinoma,BUC).Both papilloma and PUNLMP are regarded as benign tumors as they lack the cytological features of malignancy.PUNLMP generally has a low risk of progression and recurrence,while BUC is associated with marked malignant characteristics and poor prognosis.Carcinomas are further subcategorized based on the presence of muscular invasion into non-muscle-invasive BUC(NMIBC)(Stage Tis-Ta-T1)and muscle-invasive BUC(MIBC)(Stage T2-T3-T4).BUC is the ninth most common cancer worldwide.The first economic study of BUC,as well as the first real-life evidence of the current therapeutic algorithm act in the Italian context.The prevalence of the disease is approximately 10%,making it the fourth most prevalent cancer in the country.The increase in prevalence requires continuous surveillance and care,resulting in a significant burden on Italian National Health Service,making any improvement to the strategy for diagnosing and treating this disease important to the medical and scientific community.In current clinical practice,There are many methods used to detect and diagnose of bladder cancer,for example:ultrasound,bladder radiography,computed tomography(CT),nuclear magnetic resonance imaging(MRI)scan(MRI),fall off cytologic examination,DNA in situ hybridization(FISH),cystoscopy and biopsy pathologic examination and so on.But the diagnosis of BUT rely on sophisticated instruments and skilled personnel.Cystoscopy and biopsy were performed as a gold method.But this approach brings pain and fear to the patient.Moreover,cancer markers may offer the advantages of simplicity and reproducibility.At present,a number of markers have been described,such as nuclear matrix protein 22(NMP22),bladder tumor antigen(BTA),and bladder cancer specific nuclear matrix protein 4(BLCA-4).Reduced Expression of Metastasis Suppressor-1(MTSS1)Accelerates Progression of Human Bladder Uroepithelium Cell Carcinoma.Telomerase reverse transcriptase(TERT)mutations in urine might be helpful for early detection of recurrence in UBC,especially in NMIBC.Opa interacting protein 5 acts as an oncogene in bladder cancer.High Expression of Long Noncoding RNA metastasis-associated lung adenocarcinoma transcript 1(MALAT1)Indicates a Poor Prognosis and Promotes Clinical Progression and Metastasis in Bladder Cancer.Plasma fibrinogen may be a promising diagnostic and prognostic biomarker for bladder tumors.Suspected occupational bladder cancer cases phase ?polymorphisms involved in bladder carcinogen metabolism modulate bladder cancer recurrence.A meta-analysis demonstrated that miRNAs,particularly multiple miRNAs in the blood,might be novel,useful biomarkers with relatively high sensitivity and specificity and can be used for the diagnosis of bladder cancer.Preoperative Neutrophil-to-Lymphocyte Ratio(NLR)was found to be associated with pathological tumor grading,but was not associated with pathological tumor staging in patients with bladder cancer.However,the performance and robustness of these markers remain unclear.Cystatin C is the most potent inhibitor of cysteine proteinases.It is abundant in various tissues and body fluids.Previous studies revealed a correlation between high serum levels of cysteine proteinase inhibitors and poor prognosis in malignant melanoma and colorectal cancer.The association of disturbances in the ratio between cysteine proteinases and endogenous inhibitors of cysteine proteinases with malignant progression is well established.Cys-C is ubiquitously expressed in nucleated cells in tissues such as the testis,epididymis,seminal vesicle,and prostate and is then secreted into various human fluids to inhibit the activity of cysteine proteases such as papain and cathepsins B,H,K,and L.Cys-C encoded by the CST3 gene,belongs to the type two cystatin superfamily and has been extensively,encoded by the CST3 gene,belongs to the type two cystatin superfamily and has been extensively studied since it was first described in 1961.CST3 is located on the short arm of chromosome 20,spans 7.3kb,contains four exons,encodes a 120-amino acid active cysteine proteinase inhibitor,and shares several features with housekeeping genes.Cys-C is considered to function as a p53-inducible tumor suppressor and apoptotic mediator that negatively regulates cathepsin L activity during carcinogenesis.Cys-C is believed to play a critical role in the tumor suppressive function of p53,as well as in extracellular,protein homeostasis.An imbalance between Cys-C and cysteine proteinases has been observed in the pathogenesis of a broad spectrum of diseases,including cancer,such as ovarian cancer and prostate cancer.But the diagnostic role of Cys-C has been dismissed in some cancers,such as renal cell carcinoma and pancreatic tumors.Cys-C was also found to modulate the invasion of prostate cancer cells by means of the androgen receptor and MAPK/Erk2 pathways.Cys-C is also a marker for inflammation,infection.The relationship between cystatin C and the clinicopathologic features of bladder tumors is not clear.There are few studies in this area,and we try to find out whether there is a relationship between them through a retrospective statistical analysis.ObjectiveTo investigate the correlations between Cys-C levels and the patient's clinicopathological characteristics.Weather Cys-C levels can be used as a tumor marker to predict the clinicopathologic features of bladder tumor patients.MethodsA review of medical records was performed for 425 patients who were newly diagnosed with BUT and received surgical management at the Department of Urology,Qilu Hospital of Shandong University,between January 2010 and October 2014.Clinical data including patient age at the time of diagnosis,sex,smoking history,painless macroscopic hematuria,routine blood examination results(white blood cell count,platelet count,plasma fibrinogen level and so on),and other tumor characteristics were obtained from the electronic patient records at our institution.Tumor grade was assessed according to the 1998 WHO/ISUP classification,and tumor stage was evaluated using the 2002 TNM classification.We first compared pretreatment serum Cys-C levels among 425 patients.Due to the level of Cys-C is strongly influenced by glomerular filtration rate,we calculate the patient's GFR by formula,then we subgroup the patients according to GFR.The relationship between serum cystatin C level and clinicopathological features was analyzed after the effects of renal impairment on cystatin C were excluded.Results1.Association of Serum Cys-C Levels with Clinical Characteristics of BUT in all 425 patients group.We found that the levels of serum Cys-C in elder BUT patients(more than 60 years)were higher than in younger patients(P=0.013).The mean Cys-C level of patients with plasma fibrinogen levels(PFL)<2.9g/L,was significantly lower than that of patients with PFL>2.9g/L(P=0.030).2.Association between serum Cys-C levels and clinical characteristics of 321 patients with GFR?90 mg/min/1.73m2.We found that the levels of serum Cys-C in elder BUT patients(more than 60 years)were higher than that in younger patients(P= 0.000).The levels of serum Cys-C in male BUT patients were higher than in female patients(P=0.012).The mean Cys-C level of patients with PFL<2.88g/L,which was significantly lower than that of patients with PFL>2.88g/L(P=0.023).There were positive correlations between circulating Cys-C levels,age(r =0.3221,P = 0.0001)and PFL(r = 0.1665,P = 0.028)3.Association between serum Cys-C levels and clinical characteristics of 104 patients with GFR<90 mg/min/1.73m2.There were insignificant associations between the levels of serum Cys-C and clinical characteristics,such as Smoking history,Painless macroscopic hematuria,WBC count,PLT count,Tumor number,Tumor size,Pathological characteristics(all P>0.05).Even the association with age,sex and PFL.Conclusions1.Serum Cystatin C Levels is not a promising biomarker for predicting clinicopathological characteristics of bladder urothelial tumors.2.Cystatin C can be a sensitive indicator of decreased renal function.3.The age-related increase in cystatin C concentration was only partially dependent on age-related reductions in glomerular filtration rate.4.In the study of cystatin C,it is necessary to exclude the effects of lower renal function on cystatin C and then study in subgroups. |
PDF Full Text Request