Simultaneous determination of urinary CEA, ferritin and TPA in Egyptian bladder cancer patients.

Urinary carcinoembryonic antigen (CEA), ferritin (Fer) and tissue polypeptide antigen (TPA) were determined in 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract disease and 70 healthy controls). CEA was determined by the kit supplied by Roche Diagnostica (CEA EIA Doumab 60), ferritin by the Tandem-E Fer kit supplied by Hybritech and TPA by the Prolifigen TPA-IRMA kit supplied by Sangtec Medical. The results of this work revealed that combined determination of urine CEA and Fer, CEA and TPA or Fer and TPA showed higher sensitivity than determination of the individual markers. There was no significant difference between combined and individual marker determination with respect to false positivity in non-malignant urinary tract diseases. At 97% specificity, the sensitivities of urine CEA, Fer and TPA were 82.1%, 71.7% and 90.6%, respectively, while combined urine CEA & Fer, CEA & TPA and Fer & TPA showed sensitivities of 92.5%, 99.1% and 98.1%, respectively. When the specificity was related to the entire non-cancer group (patients with benign urinary tract diseases and normal controls), some reduction in the sensitivities of the combined markers was noted compared to the normal group only. In conclusion, combined determination of urine markers is superior to determination of individual markers in the diagnosis of bladder cancer.     

Diagnosis of bladder cancer with urinary cytology, immunocytology and DNA-image-cytometry.

DNA-image-cytometry and antibodies directed against the Lewis X- and the 486p 3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for the detection of bladder cancer. Cytology, immunocytology and DNA-image-cytometry were performed in spontaneously voided urine samples and barbotage bladder washings from 71 patients. The DNA content was determined using the CM-1 Cytometer according to the recommendation of the ESCAP Consensus Report on Standardization of DNA-image-cytometry (1995). For immunocytological examination we used the monoclonal anti Lewis X antibody P-12 and antibody 486p 3/12. All patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or transurethral resection was done. Histological findings revealed 31 patients with transitional cell carcinomas of different stages and grades of malignancy. 40 patients had various benign diseases of the urinary bladder. Cytology yielded a sensitivity of 68% and a specificity of 100%. DNA aneuploidy was detected in 81% of cancer patients with a specificity of 100%. By combination of these two methods the overall sensitivity increased to 87%. Immunocytology with Lewis X and 486p 3/12 antibodies showed reactivity in 84% and 87% in combination with a specificity of 80% and 70%, respectively. By combining urinary cytology, immunocytology and/or DNA-image-cytometry the overall sensitivity increased to 94% with no change in specificity. DNA-image-cytometry should be used to evaluate particularly urothelial cells suspicious for malignancy in urinary specimens. Because of low specificity the monoclonal antibodies against Lewis X- and 486p 3/12 antigens are not helpful in screening for bladder cancer. Nevertheless, their high sensitivity may justify their use in case DNA image cytometry is not available and in the follow up of patients with transitional cell carcinoma.     

血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断价值分析

摘要 目的：探讨与分析血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断价值。方法：2019年8月到2022年5月选择在本院诊治的消化道恶性肿瘤患者150例作为消化道恶性肿瘤组,同期选择在本院体检的健康人群150例作为健康组。采集两组人群的血清癌胚抗原（CEA）、糖类抗原19-9（CA19-9）、C-反应蛋白（CRP）含量,调查患者的病理特征并判断诊断价值。结果：消化道恶性肿瘤组的血清CEA、CA19-9、CRP含量都高于健康组（P<0.05）。消化道恶性肿瘤组的CEA、CA19-9、CRP阳性率为54.7 %、58.7 %、60.7 %,高于健康组的3.3 %、4.0 %、4.7 %（P<0.05）。在消化道恶性肿瘤组中,不同组织学分化、临床分期、淋巴结转移患者的血清CEA、CA19-9、CRP含量对比有差异（P<0.05）。血清CEA、CA19-9联合CRP诊断为阳性113例,在健康组中诊断为阳性3例,血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断敏感性与特异性分别为75.3 %（113/150）和98.0 %（147/150）。结论：消化道恶性肿瘤患者多伴随有血清CEA、CA19-9、CRP的高表达,病理特征与血清CEA、CA19-9、CRP含量存在相关性,血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断敏感性与特异性都比较好。     

AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma.

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.     

Endoscopic OCT with forward‐looking probe: clinical studies in urology and gastroenterology

In the current paper we present results of application of endoscopic time‐domain OCT (EOCT) with lateral scanning by forward looking miniprobe. We analysed material of clinical studies of 554 patients: 164 patients with urinary bladder pathology, and 390 with gastrointestinal tract pathology. We reviewed the materials obtained in different clinics using the OCT device elaborated at the Institute of Applied Physics. We demonstrate results of EOCT application in detection of early cancer and surgery guidance, examples of combined use of OCT and fluorescence imaging. As a result, we show the diagnostic accuracy of EOCT in specific clinical tasks. The sensitivity of EOCT cancer determination in Barrett's esophagus is from 71% to 85% at different stages of neoplasia with specificity 68% for all stages. As for bladder carcinoma, the sensitivity and specificity are 85% and 68%, respectively. In colon dysplasia EOST demonstrates high efficacy: sensitivity 92% and specificity 84%. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

The diagnostic accuracy of sputum and urine cytology

The diagnostic accuracies of sputum and urinary cytology were examined in series spanning more than 20 years. The sensitivity and respiratory tract cytology in 1,289 patients with subsequently proven lung cancer was 69% while that or urine cytology in 860 patients with urinary tract cancer was 77%. The specificities were 96% for lung cancer and 97% for urinary tract cancer. Neither procedure was widely used for routine screening, but diagnostic cytology played an important part in providing a definite morphologic diagnosis in many of these cases. Urinary cytology was also very effective in the follow-up of patients with treated bladder cancer because of its high sensitivity for detecting carcinoma in situ.     

Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers

The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer), owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67-80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease.     

Cytokeratins as serum markers in egyptian bladder cancer. A comparison of CYFRA 21-1, TPA and TPS

Cytokeratins (CKs) have been shown to be overexpressed in bladder cancer and to be valuable as tumor markers. The present study was designed to evaluate the single and combined use of three cytokeratin fragments, CYFRA 21-1, TPA, and TPS, in serum of Egyptian bladder cancer patients. The study subjects comprised 40 healthy controls, 30 patients with benign bladder diseases, and 60 patients with histologically confirmed primary bladder cancer. The cutoff was set at 95% specificity versus benign bladder diseases, resulting in cutoff values of 2.93 ng/mL for CYFRA 21-1, 158 U/L for TPA and 143.7 ng/mL for TPS. With 41% true positive results CYFRA 21-1 had a higher sensitivity than TPA (32%) and TPS (27%). Evaluation by histological findings revealed a highest sensitivity of CYFRA 21-1 (46%) in transitional cell carcinoma (TCC) followed by TPA (27%) and TPS (21%). Also in adenocarcinoma CYFRA 21-1 showed the highest sensitivity (38%) followed by TPA (32%) and TPS (28%). A high percentage (41.6%) of Egyptian bladder cancers is represented by squamous cell carcinoma (SCC). In this population TPS showed the highest sensitivity (69%), followed by CYFRA 21-1 (54%) and TPA (41 %). The sensitivity of each of the three markers increased with advancing tumor stage and increasing tumor grade. Combined use of two of the three markers did not raise the sensitivities obtained by single determination of CYFRA 21-1. The present study suggests that serum CYFRA 21-1 could be a marker of choice in bladder cancer.     

Multiplexed quantification of 63 proteins in human urine by multiple reaction monitoring-based mass spectrometry for discovery of potential bladder cancer biomarkers

Three common urological diseases are bladder cancer, urinary tract infection, and hematuria. Seventeen bladder cancer biomarkers were previously discovered using iTRAQ - these findings were verified by MRM-MS in this current study. Urine samples from 156 patients with hernia (n=57, control), bladder cancer (n=76), or urinary tract infection/hematuria (n=23) were collected and subjected to multiplexed LC-MRM/MS to determine the concentrations of 63 proteins that are normally considered to be plasma proteins, but which include proteins found in our earlier iTRAQ study. Sixty-five stable isotope-labeled standard proteotypic peptides were used as internal standards for 63 targeted proteins. Twelve proteins showed higher concentrations in the bladder cancer group than in the hernia and the urinary tract infection/hematuria groups, and thus represent potential urinary biomarkers for detection of bladder cancer. Prothrombin had the highest AUC (0.796), with 71.1% sensitivity and 75.0% specificity for differentiating bladder cancer (n=76) from non-cancerous (n=80) patients. The multiplexed MRM-MS data was used to generate a six-peptide marker panel. This six-peptide panel (afamin, adiponectin, complement C4 gamma chain, apolipoprotein A-II precursor, ceruloplasmin, and prothrombin) can discriminate bladder cancer subjects from non-cancerous subjects with an AUC of 0.814, with a 76.3% positive predictive value, and a 77.5% negative predictive value. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.     

Tissue and serum TPA in subjects at risk for bladder cancer

We tested the presence of tumour polypeptide antigen (TPA) in lower urinary tract cells from 59 workers exposed to known bladder carcinogens and from 30 control subjects. We then correlated immunocytological expression and serum TPA levels. Lower urinary tract cells from 31 subjects gave either moderately or strongly positive immunocytological stains. Five also had high serum TPA. The detection of TPA by cytology and in serum differed significantly in workers exposed to cancer agents and the control group.     

血清CEA、CA19-9、CYFRA21-1与结直肠腺癌的相关性分析

目的:探究血清癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原19-9、细胞角蛋白19片段(cytokeratin19 fragements,CYFRA21-1)与结直肠腺癌的病理相关性。方法:选择于我院接受治疗的80例结直肠腺癌患者为病例组,选择同期于我院接受治疗的50例良性结直肠病变患者为良性对照组,选择我院体格检查的50例健康个体为对照组,分别采集三组个体的血样并进行CEA、CA19-9以及CYFRA21-1水平的检测,并比对三组个体上述因子阳性表达率、因子水平,同时分析三种因子同结直肠腺癌患者TNM分期相关性,最后探究三种因子对结直肠腺癌的诊断价值。结果:(1)以CEA≥2.805μg/L、CA19-9≥39 U/m L、CYFR21-1≥3.3 ng/mL为临界值,结果显示病例组CEA阳性率51.25%,CA19-9阳性率31.25%,CYFR21-1阳性率40.00%,明显高于良性组的10.00%、20.00%和10.00%,高于对照组的8.00%、12.00%和2.00%(P<0.05);(2)比较显示病例组患者的CEA、CA19-9以及CYFR21-1水平明显高于良性对照组以及对照组(P<0.05),良性对照组CEA、CA19-9以及CYFR21-1水平明显高于对照组(P<0.05);(3)比较显示IV期结直肠腺癌患者CEA、CA19-9以及CYFRA21-1水平明显高于III期以及I+II期(P<0.05),III期三种因子水平明显高于I+II期(P<0.05);(4)CEA对结直肠腺癌诊断一致性71.25%,灵敏度65.00%,特异度90.00%;CA19-9诊断一致性46.25%,灵敏度35.00%,特异度80.00%;CYFRA21-1诊断一致性55.00%,灵敏度46.67%,特异度80.00%;联合诊断一致性95.00%,灵敏度95.00%,特异度95.00%。结论:血清CEA、CA19-9以及CYFRA21-1对结直肠腺癌具有较明确的诊断价值,不同病理分期患者中表达差异明显,可以考虑将联合诊断作为结直肠腺癌鉴别方式之一,推广于临床中。     

Application of urinary mutagen testing to detect workplace hazardous exposure and bladder cancer

The objectives of this biochemical epidemiologic case-control study were to evaluate urinary mutagen testing for occupational exposure assessment, and for possible screening for bladder cancer in the workplace. Thirty-seven patients (19 bladder cancer cases and 18 controls) completed a questionnaire. Two urine samples, i.e. a work sample taken while at work, and a home sample, were requested from each patient. Twenty-six patients (17 cases and 9 controls) gave a total of 47 24-h urine samples for mutagenicity testing by the Ames test. A positive Ames test was found to be associated significantly with current occupation with hazardous exposure (odds ratio = 3.7, 95%CI 1.1–12.9), and non-significantly with bladder cancer (odds ratio = 1.8, 95%CI 0.5–7.1). Our results show that the urinary Ames test has the potential of being used as a surveillance for current workplace hazardous exposure (sensitivity = 52%, specificity = 77%, positive predictive value = 72%, negative predictive value = 59%, positive likelihood ratio = 2.3), but not as a screening test for bladder cancer cases (sensitivity = 42%, specificity = 71%, positive predictive value = 3%, negative predictive value = 98%, positive likelihood ratio = 1.5).     

Significance of CA 72.4 serum levels in gastrointestinal diseases

In order to evaluate the usefulness of Ca 72.4 tumor associated antigen assay in gastrointestinal diseases, we have studied 751 patients suffering from benign (376) and neoplastic (375) digestive diseases and 305 normal controls. The cut-off point was fixed at 6 U/ml. The Ca 72.4 assay, with the proposed method, provides additional information only in gastric cancers; the positivity of the marker in gastric neoplasms is 38.4% and the specificity vs gastric ulcers and atrophic gastritis is 99%. In six patients with gastric cancer, the Ca 72.4 is the only positive test. The most striking observation to be made from the current study is a no good sensitivity of the marker for gastrointestinal cancers (29.6% vs 35.7 and 37.6% for CEA and Ca 19-9 respectively), but rather the excellent specificity of the Ca 72.4 immunoassay with respect to being gastrointestinal diseases (98.7%), vs values of specificity for CEA and Ca 19-9 of 94 and 92%. In conclusion, the high specificity of this marker for gastrointestinal neoplasms may be very interesting in follow-up studies. In fact, an elevation of serum levels of Ca 72.4 should always be taken seriously.     

Diagnostic evaluation of alanine aminopeptidase as serum marker for detecting cancer.

Alanine aminopeptidase (AAP), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) were measured in 40 patients with breast and thyroid cancer and in 40 patients suffering from benign tumors and benign noninflammatory diseases. AAP activity was significantly increased (P < 0.001) in all cancer patients considered together. TPA shows a remarkable diagnostic sensitivity but a low specificity. For CEA an inverse situation is observed. Evaluation of the predictive value of the assay of AAP revealed a sufficient sensitivity, a good specificity, a sufficient predictive value of both positive and negative results, and a good efficiency. We believe that the test, if supported by other information, can be useful in the diagnosis of breast and thyroid cancer.     

ELISA定量分析尿液BLCA-1/-4水平诊断膀胱癌的临床价值分析

目的:探讨膀胱癌患者尿液膀胱特异性核基质蛋白(bladder cancer specific nuclear matrix proteins,BLCA)-1/-4水平及其临床应用价值。方法:本研究纳入38例膀胱癌患者、40例正常对照组。采集受试者尿液样本,通过竞争性酶联免疫吸附法(enzymelinked immunosorbent assay,ELISA)定量分析尿液中BLCA-1和BLCA-4的水平,绘制受试者工作曲线,确定cut-off值。结果:膀胱癌患者尿液BLCA-1/-4水平均显著高于对照组(P0.001);当cut-off值取0.859 ng/mL时,BLCA-1诊断膀胱癌的敏感性和特异性分别为71%(27/38)、90%(36/40)。肌层浸润性膀胱癌患者尿液BLCA-1较非肌层浸润性膀胱癌患者水平显著升高(P0.001),但不同分级膀胱癌患者尿液BLCA-4水平无显著差异(P0.05)。高级别膀胱癌患者尿液BLCA-4水平较低级别膀胱癌患者显著升高(P0.05),但不同分期膀胱癌患者尿液BLCA-4水平无显著差异(P0.05)。以cut-off为0.859 ng/mL时,BLCA-1诊断膀胱癌的敏感性和特异性分别为71%(27/38)、90%(36/40)。以cut-off为0.620 ng/mL时,BLCA-4诊断膀胱癌的敏感性和特异性分别为76.3%(29/38)、97.5%(39/40)。联合检测尿液BLCA-1和BLCA-4诊断膀胱癌的敏感性和特异性分别为84.2%(32/38)和100%(40/40),准确度为0.923(77/78),阳性预测值为100%(32/32),阴性预测值为86.9%(40/46)以及YOUDEN指数分别为0.842。结论:膀胱癌患者尿液BLCA-1和BLCA-4水平显著升高,且敏感性和特异性均较高。联合检测尿液BLCA-1和BLCA-4较单一检测用于诊断膀胱癌的临床应用价值更高。     

Comparative analysis of certain metals and tumor markers in bronchopulmonary cancer and colorectal cancers. Metals and tumor markers in the neoplastic process

Carcinogenic metal levels in serum and tissue samples were measured in patients with bronchopulmonary or colorectal cancer. The cadmium and nickel tissue levels in the patients with lung cancer were significantly higher than in the controls. A statistical correlation was found between chromium and cadmium, as well as between cadmium and nickel in patients with colorectal cancer. In addition, prior to the operation, the tumor markers alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (Ca 19-9), polypeptide histidio antigen (TPA) and ferritin were analyzed. Their average concentrations were correlated with the existing concentrations of the metals. This was done for both types of cancer. Tumor marker detection showed an increase of CEA and TPA in patients with colorectal cancer. A statistical correlation was observed between AFP and zinc tumor tissue.     

血清及胸腔积液中CA19-9、SCC-Ag及CYFRA21-1对肺癌诊断意义的对比研究

目的:探讨肺癌患者血清及胸腔积液中的糖蛋白抗原19-9(CA19-9)、鳞状细胞癌抗原(SCC-Ag)和细胞角蛋白19片段(CYFRA21-1)对肺癌的诊断意义。方法:选取2016年1月到2017年6月在我院接受治疗的肺癌患者67例作为肺癌组,另选取我院同期收治的肺良性病变患者55例纳入良性病变组。采用电化学发光法检测并对比两组患者血清及胸腔积液中的CA19-9、SCC-Ag和CYFRA21-1水平,比较所有研究对象血清及胸腔积液中CA19-9、SCC-Ag和CYFRA21-1的阳性率并分析其诊断价值。结果:肺癌组患者血清及胸腔积液中的CA19-9、SCC-Ag和CYFRA21-1水平显著高于良性病变组,有统计学差异(P0.05)。CA19-9、SCC-Ag和CYFRA21-1在胸腔积液中的阳性率高于在血清中的阳性率,有统计学差异(P0.05)。胸腔积液中CA19-9、SCC-Ag和CYFRA21-1单项检测对肺癌的灵敏度显著高于血清检测,血清及胸腔积液中CA19-9、SCC-Ag和CYFRA21-1三项联合检测的灵敏度、特异性、阳性预测值均高于单项检测,差异均有统计学意义(P0.05)。结论:肺癌患者血清及胸腔积液中CA19-9、SCC-Ag和CYFRA21-1呈现高表达,三项指标联合检测可提高诊断肺癌的灵敏度、特异性和阳性预测值。     

Granulocyte-macrophage-colony stimulating factor in patients with colorectal cancer

Granulocyte-macrophage-colony stimulating factor (GM-CSF) belongs to the group of glycoproteins called colony-stimulating factors (CSFs). It has been shown that the activity of CSFs is not limited to the hematopoietic cells but can also affect the proliferation of colon carcinoma cell lines. The purpose of this investigation was to compare the serum level of GM-CSF in colorectal cancer patients to a control group, to assess the level of GM-CSF in relation to the level of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), and to define the sensitivity, the specificity and the predictive values of GM-CSF in colorectal cancer. In this study, the serum level of tumour markers was measured in 30 patients with colorectal cancer and in 20 healthy subjects. GM-CSF was assayed using ELISA system, CEA and CA 19-9 were measured by MEIA. The serum levels of CEA, CA 19-9 and GM-CSF were higher in the patients with colorectal cancer than in the control group. The sensitivities of CEA (63%) and CA 19-9 (56%) were lower than the GM-CSF sensitivity (80%). The specificities of tumour markers were 70% (CEA, GM-CSF) and 75% for CA 19-9. The GM-CSF predictive v values were higher than the CEA and CA 19-9 values. These results suggest that GM-CSF may be useful as tumour marker in colorectal cancer, but further studies are needed.     

荧光原位杂交应用于尿路上皮癌尿液早期诊断的研究进展

尿路上皮癌（urothelial carcinoma,uc）是泌尿系统最常见恶性肿瘤之一,早期诊断是提高该类疾病疗效的关键所在,荧光原位杂交（fluorescencein situ hybridization,FISH）通过尿液来检测UC,具有快速、无创伤性、敏感度高和特异性强等优点。FISH提高了尿细胞学在低级别或浅表性膀胱UC诊断的敏感性,且减少了血尿、尿路感染及膀胱内灌注治疗等对细胞形态的影响而引起的假阳性,提高检测的特异性。对于诊断上尿路UC,FISH的敏感性与特异性更高。膀胱UC患者9号染色体p16抑癌基因丢失与复发明显相关。FISH既能预测膀胱UC的复发性,更能监测UC的复发,但仍需大样本、多中心的前瞻性研究。本文将FISH在膀胱UC、上尿路UC早期诊断以及膀胱UC术后监测等方面的临床应用研究报道进行综述。     

A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer

Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These datashow that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.