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The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma.

ABSTRACT: Renal cancer is frequently asymptomatic until late stages of the disease and it has a poor prognosis when not discovered early. AQP1 and PLIN2 are recently discovered, sensitive urine biomarkers of clear cell and papillary kidney cancer. We validated these biomarkers in a second cohort of patients and determined the effect of common kidney diseases on specificity.Urine samples were obtained from 36 patients with clear cell or papillary kidney cancer, 43 controls, 44 patients with documented urinary tract infection, 24 diagnosed with diabetic nephropathy and 18 diagnosed with glomerulonephritis. Urine levels of AQP1 and PLIN2 normalized to urine creatinine were determined by a sensitive, specific Western blot procedure.Compared with controls, urine AQP1 and PLIN2 levels in patients with kidney cancer were 23-fold and fourfold greater, respectively, and they decreased 83% to 84% after tumor excision. There was a linear correlation between urine AQP1 and PLIN2 levels, and tumor size (each p <0.001). Urine AQP1 and PLIN2 levels in patients with kidney cancer were 11 to 23-fold and 17 to 25-fold greater, respectively, than in patients with the common kidney diseases.The ability of urine AQP1 and PLIN2 to identify patients with kidney cancer compared to controls was validated in a second cohort of patients. Common kidney diseases do not adversely increase urine AQP1 and PLIN2 levels or decrease their specificity to screen for renal cancer.

SUBMITTER: Morrissey JJ

PROVIDER: S-EPMC3720141 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma.

Morrissey Jeremiah J JJ Kharasch Evan D ED

The Journal of urology 20121112 5

<h4>Purpose</h4>Renal cancer is frequently asymptomatic until late stages of the disease and it has a poor prognosis when not discovered early. AQP1 and PLIN2 are recently discovered, sensitive urine biomarkers of clear cell and papillary kidney cancer. We validated these biomarkers in a second cohort of patients and determined the effect of common kidney diseases on specificity.<h4>Materials and methods</h4>Urine samples were obtained from 36 patients with clear cell or papillary kidney cancer, ...[more]

PMID: 23154208

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Project description:ImportanceHistorically, early detection of small asymptomatic kidney tumors presages better patient outcome. Screening for asymptomatic renal tumors by abdominal imaging is not cost-effective and cannot reliably distinguish benign from malignant tumors.ObjectiveThis investigation evaluated the clinical utility, sensitivity, and specificity of urine aquaporin-1 (AQP1) and perilipin-2 (PLIN2) concentrations as unique, noninvasive biomarkers to diagnose malignant clear cell or papillary renal cell carcinoma (RCC) in a screening paradigm.Design, setting, and participantsFrom February through December 2012, urine samples were obtained from 720 patients undergoing routine abdominal computed tomography (CT) (screening population), 80 healthy controls, and 19 patients with pathologically confirmed RCC.Main outcomes and measuresUrine AQP1 and PLIN2 concentrations were measured by sensitive and specific enzyme-linked immunosorbent assay and Western blot procedures, respectively, in all groups. In the otherwise asymptomatic screening population, the absence or presence of a renal mass and RCC were verified by abdominal CT and by postnephrectomy pathologic diagnosis, respectively.ResultsUrine AQP1 and PLIN2 concentrations were significantly higher (all P < .001) in the 19 patients with known RCC (AQP1 median [95% CI], 225.0 [121.0-450.0] ng/mg urine creatinine; and PLIN2 median [95% CI], 37.8 [22.8-83.7] absorbance units/mg creatinine) than in the 80 healthy controls (AQP1 median [95% CI], 1.1 [0.9-1.3] ng/mg urine creatinine; and PLIN2 median [95% CI], 3.1 [2.4-3.7] absorbance units/mg creatinine) and the 720 patient screening population (AQP1 median [95% CI], 0.5 [0.0-1.0] ng/mg urine creatinine; and PLIN2 median [95% CI], 0 [0-0] absorbance units/mg creatinine). The area under the receiver operating characteristic curve for urine AQP1 and PLIN2 concentrations individually or in combination was 0.990 or greater, with 95% or greater sensitivity and 91% or greater specificity compared with controls or the screening population. Of the 720 screened patients, 3 had biomarker concentrations suggestive of RCC and were found to have an imaged renal mass by CT. Two of the patients had pathologically confirmed RCC in further evaluation.Conclusions and relevanceThese results demonstrate the clinical utility, specificity, and sensitivity of urine AQP1 and PLIN2 to diagnose RCC. These tumor-specific proteins have high clinical validity and substantial potential as specific diagnostic and screening biomarkers for clear cell or papillary RCC and in the differential diagnosis of imaged renal masses.

Project description:BACKGROUND:Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). Aquaporin 9 (AQP9) is involved in many immune-related signals; however, its role in ccRCC remains to be elucidated. This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. METHODS:A total of 913 ccRCC patients with available RNA-sequence data from the Cancer Genome Atlas (TCGA) database and Fudan University Shanghai Cancer Center (FUSCC) were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained and validated using multiple datasets. A partial likelihood test from Cox regression analysis was developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess survival. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of AQP9 using area under the curve (AUC) score. Functional enrichment analyses and immune infiltration analysis were used to describe significantly involved hallmark pathways of hub genes. RESULTS:Significantly elevated transcriptional and proteomic AQP9 expressions were found in ccRCC samples. Increased AQP9 mRNA expression was significantly associated with advanced clinicopathological parameters and correlated with shorter PFS and OS in TCGA and FUSCC cohorts (p?<?0.001). ROC curves suggested the significant diagnostic and prognostic ability of AQP9 (PFS, AUC?=?0.823; OS, AUC?=?0.828). Functional annotations indicated that AQP9 is involved in the most significant hallmarks including complement, coagulation, IL6/JAK-STAT3, inflammatory response and TNF-alpha signaling pathways. CONCLUSION:Our study revealed that elevated AQP9 expression was significantly correlated with aggressive progression, poor survival and immune infiltrations in ccRCC patients, and we validated its prognostic value in a real-world cohort. These data suggest that AQP9 may act as an oncogene and a promising prognostic marker in ccRCC.

Project description:ObjectivesTo develop a CT-based radiomics model and a combined model for preoperatively discriminating infiltrative renal cell carcinoma (RCC) and pyelocaliceal upper urinary tract urothelial carcinoma (UTUC), which invades the renal parenchyma.Materials and methodsEighty patients (37 pathologically proven infiltrative RCCs and 43 pathologically proven pyelocaliceal UTUCs) were retrospectively enrolled and randomly divided into a training set (n = 56) and a testing set (n = 24) at a ratio of 7:3. Traditional CT imaging characteristics in the portal venous phase were collected by two radiologists (SPH and ZXL, who have 4 and 30 years of experience in abdominal radiology, respectively). Patient demographics and traditional CT imaging characteristics were used to construct the clinical model. The radiomics score was calculated based on the radiomics features extracted from the portal venous CT images and the random forest (RF) algorithm to construct the radiomics model. The combined model was constructed using the radiomics score and significant clinical factors according to the multivariate logistic regression. The diagnostic efficacy of the models was evaluated using receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC).ResultsThe RF score based on the eight validated features extracted from the portal venous CT images was used to build the radiomics model. Painless hematuria as an independent risk factor was used to build the clinical model. The combined model was constructed using the RF score and the selected clinical factor. Both the radiomics model and combined model showed higher efficacy in differentiating infiltrative RCC and pyelocaliceal UTUC in the training and testing cohorts with AUC values of 0.95 and 0.90, respectively, for the radiomics model and 0.99 and 0.90, respectively, for the combined model. The decision curves of the combined model as well as the radiomics model indicated an overall net benefit over the clinical model. Both the radiomics model and the combined model achieved a notable reduction in false-positive and false-negativerates, resulting in significantly higher accuracy compared to the visual assessments in both the training and testing cohorts.ConclusionThe radiomics model and combined model had the potential to accurately differentiate infiltrative RCC and pyelocaliceal UTUC, which invades the renal parenchyma, and provide a new potentially non-invasive method to guide surgery strategies.

Dataset Information

The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma.

Publications

The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma.

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