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Urinary biomarkers for the early diagnosis of kidney cancer.

ABSTRACT: To test the hypothesis that increased tumor expression of proteins such as aquaporin-1 (AQP1) and adipophilin (ADFP) in patients with renal cancer would result in increased urine AQP1 and ADFP excretion.Prenephrectomy and postnephrectomy (pseudocontrol) urine samples were collected from 42 patients with an incidental radiographically discovered renal mass and presurgical presumptive diagnosis of kidney cancer from July 8, 2008, through March 10, 2009. Also enrolled were 15 control patients who underwent nonrenal surgery and 19 healthy volunteers. Urine AQP1 and ADFP concentrations normalized to urine creatinine were determined by sensitive and specific Western blot assays.Mean +/- SD preexcision urine AQP1 and ADFP concentrations (76+/-29 and 117+/-74 arbitrary units, respectively) in patients with a pathologic diagnosis of clear cell (n=22) or papillary (n=10) cancer were significantly greater than in patients with renal cancer of nonproximal tubule origin, control surgical patients, and healthy volunteers (combined values of 0.1+/-0.1 and 1.0+/-1.6 arbitrary units, respectively; n=44; P<.001). The AQP1 and ADFP concentrations decreased 88% to 97% in the 25 patients with clear cell or papillary cancer who provided postnephrectomy follow-up urine samples. In patients with clear cell and papillary carcinoma, a linear correlation (Spearman) was found between tumor size and preexcision urine AQP1 or ADFP concentration (r=0.82 and 0.76, respectively; P<.001 for each).Urine AQP1 and ADFP concentrations appear to be sensitive and specific biomarkers of kidney cancers of proximal tubule origin. These biomarkers may be useful to diagnose an imaged renal mass and screen for kidney cancer at an early stage.clinicaltrials.gov Identifier: NCT00851994.

SUBMITTER: Morrissey JJ

PROVIDER: S-EPMC2861969 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Urinary biomarkers for the early diagnosis of kidney cancer.

Morrissey Jeremiah J JJ London Amy N AN Luo Jingqin J Kharasch Evan D ED

Mayo Clinic proceedings 20100407 5

<h4>Objective</h4>To test the hypothesis that increased tumor expression of proteins such as aquaporin-1 (AQP1) and adipophilin (ADFP) in patients with renal cancer would result in increased urine AQP1 and ADFP excretion.<h4>Patients and methods</h4>Prenephrectomy and postnephrectomy (pseudocontrol) urine samples were collected from 42 patients with an incidental radiographically discovered renal mass and presurgical presumptive diagnosis of kidney cancer from July 8, 2008, through March 10, 200 ...[more]

PMID: 20375178

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Project description:MicroRNA (miRNA or miR) is stably present in plasma. It has been reported that miRNA could be used for detecting cancer. Circulating miRNAs are being increasingly recognized as powerful biomarkers in a number of different pathologies, including in breast cancer. The aim of the current study was to establish and validate miRNA sets that are useful for the early diagnosis of breast cancer. Specifically, the current study intended to determine whether miRNA biomarkers were tumor-specific and to statistically verify whether circulating miRNA analysis could be used for breast cancer diagnosis. In the present study, a total of nine candidate miRNA biomarkers were selected by examining reference miRNAs associated with the generation and progression of breast cancer to identify novel miRNAs that could be used to detect early breast cancer. A total of 226 plasma samples from patients with breast cancer were used. In addition, 146 plasma healthy samples were used as non-cancer controls. These samples were divided into training and validation cohorts. The training cohort was used to identify a combination of miRNA that could detect breast cancer. The validation cohort was used to validate this combination of miRNA. Total RNAs were isolated from collected samples. A total of 9 miRNAs were quantified using reverse-transcription quantitative PCR. A total of nine candidate miRNA expression levels were compared between patients with breast cancer and healthy controls. It was indicated that combinations of two or more of the nine miRNAs could detect breast cancer with higher accuracy than the use of a single biomarker. As a representative example, combinations of four miRNAs (miR-1246+miR-206+miR-24+miR-373) of the nine miRNAs had a sensitivity of 98%, a specificity of 96% and an accuracy of 97% for breast cancer detection in the validation cohort. The results of the present study suggest that multiple miRNAs could be used as potential biomarkers for early diagnosis of breast cancer. These biomarkers are expected to overcome limitations of mammography when used as an auxiliary diagnosis of mammography.

Project description:BackgroundHump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites.MethodsWe conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming.ResultsThere were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points.ConclusionssCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.

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Urinary biomarkers for the early diagnosis of kidney cancer.

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Urinary biomarkers for the early diagnosis of kidney cancer.

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