Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3349-3359 |
| Number of pages | 11 |
| Journal | Clinical Cancer Research |
| Volume | 17 |
| Issue number | 10 |
| DOIs | |
| State | Published - May 15 2011 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Urinary glycoprotein biomarker discovery for bladder cancer detection using LC/MS-MS and label-free quantification. / Yang, Na; Feng, Shun; Shedden, Kerby; Xie, Xiaolei; Liu, Yashu; Rosser, Charles J.; Lubman, David M.; Goodison, Steven.
In: Clinical Cancer Research, Vol. 17, No. 10, 15.05.2011, p. 3349-3359.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Urinary glycoprotein biomarker discovery for bladder cancer detection using LC/MS-MS and label-free quantification
AU - Yang, Na
AU - Feng, Shun
AU - Shedden, Kerby
AU - Xie, Xiaolei
AU - Liu, Yashu
AU - Rosser, Charles J.
AU - Lubman, David M.
AU - Goodison, Steven
PY - 2011/5/15
Y1 - 2011/5/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79956044485&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79956044485&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-10-3121
DO - 10.1158/1078-0432.CCR-10-3121
M3 - Article
C2 - 21459797
AN - SCOPUS:79956044485
VL - 17
SP - 3349
EP - 3359
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 10
ER -