Urinary glycoprotein biomarker discovery for bladder cancer detection using LC/MS-MS and label-free quantification.

نویسندگان

  • Na Yang
  • Shun Feng
  • Kerby Shedden
  • Xiaolei Xie
  • Yashu Liu
  • Charles J Rosser
  • David M Lubman
  • Steven Goodison
چکیده

BACKGROUND Cancers of the urinary bladder are the fifth most commonly diagnosed malignancy in the United States. Early clinical diagnosis of bladder cancer remains a major challenge, and the development of noninvasive methods for detection and surveillance is desirable for both patients and health care providers. APPROACH To identify urinary proteins with potential clinical utility, we enriched and profiled the glycoprotein component of urine samples by using a dual-lectin affinity chromatography and liquid chromatography/tandem mass spectrometry platform. RESULTS From a primary sample set obtained from 54 cancer patients and 46 controls, a total of 265 distinct glycoproteins were identified with high confidence, and changes in glycoprotein abundance between groups were quantified by a label-free spectral counting method. Validation of candidate biomarker alpha-1-antitrypsin (A1AT) for disease association was done on an independent set of 70 samples (35 cancer cases) by using an ELISA. Increased levels of urinary A1AT glycoprotein were indicative of the presence of bladder cancer (P < 0.0001) and augmented voided urine cytology results. A1AT detection classified bladder cancer patients with a sensitivity of 74% and specificity of 80%. SUMMARY The described strategy can enable higher resolution profiling of the proteome in biological fluids by reducing complexity. Application of glycoprotein enrichment provided novel candidates for further investigation as biomarkers for the noninvasive detection of bladder cancer.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Imaging, Diagnosis, Prognosis Urinary Glycoprotein Biomarker Discovery for Bladder Cancer Detection Using LC/MS-MS and Label-Free Quantification

Background: Cancers of the urinary bladder are the fifth most commonly diagnosed malignancy in the United States. Early clinical diagnosis of bladder cancer remains amajor challenge, and the development of noninvasivemethods for detection and surveillance is desirable for both patients and health care providers. Approach: To identify urinary proteins with potential clinical utility, we enriched...

متن کامل

Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach

INTRODUCTION Breast cancer is a complex heterogeneous disease and is a leading cause of death in women. Early diagnosis and monitoring progression of breast cancer are important for improving prognosis. The aim of this study was to identify protein biomarkers in urine for early screening detection and monitoring invasive breast cancer progression. METHOD We performed a comparative proteomic a...

متن کامل

Is label-free LC-MS/MS ready for biomarker discovery?

Label-free LC-MS methods are attractive for high-throughput quantitative proteomics, as the sample processing is straightforward and can be scaled to a large number of samples. Label-free methods therefore facilitate biomarker discovery in studies involving dozens of clinical samples. However, despite the increased popularity of label-free workflows, there is a hesitance in the research communi...

متن کامل

LC-MS/MS quantification of Zn-alpha2 glycoprotein: a potential serum biomarker for prostate cancer.

BACKGROUND Zn-alpha2 glycoprotein (ZAG) is a relatively abundant glycoprotein that has potential as a biomarker for prostate cancer. We present a high-flow liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring serum ZAG concentrations by proteolytic cleavage of the protein and quantification of a unique peptide. METHODS We selected the ZAG tryptic peptide (147)EIPAWVP...

متن کامل

Quantitative Label-Free Proteomics for Discovery of Biomarkers in Cerebrospinal Fluid: Assessment of Technical and Inter-Individual Variation

BACKGROUND Biomarkers are required for pre-symptomatic diagnosis, treatment, and monitoring of neurodegenerative diseases such as Alzheimer's disease. Cerebrospinal fluid (CSF) is a favored source because its proteome reflects the composition of the brain. Ideal biomarkers have low technical and inter-individual variability (subject variance) among control subjects to minimize overlaps between ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 17 10  شماره 

صفحات  -

تاریخ انتشار 2011