Pattern analysis of serum proteome distinguishes renal cell carcinoma from other urologic diseases and healthy persons

Won, Yonggwan; Song, Ho‐Jun; Kang, Taek Won; Kim, Jung-Ja; Han, Byoung-Don; Lee, Seungwon

doi:10.1002/pmic.200300590

Cited by 103 publications

(56 citation statements)

References 10 publications

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“…Indeed, SELDI-TOF MS has also been performed to identify biomarker proteins for early detection of RCC. Two studies describe protein profiling of serum with SELDI-TOF MS. 8,9 Tolson et al 8 reported a peak cluster at a mass-to-charge ratio (m/z) of approximately 11 000 from serum amyloid a-1 and variants, which was 100% specific for RCC compared to HC, although not very sensitive (detection in eight of 25 patients). Five m/z values of 3900, 4107, 4153, 5352 and 5987 were reported by Won et al 9 in a classification tree separating RCC from healthy and non-RCC urologic disease, with sensitivities and specificities ranging from 80 to 100%.…”

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confidence: 99%

Validation of SELDI-TOF MS serum protein profiles for renal cell carcinoma in new populations

Engwegen

Mehra

Haanen

et al. 2007

Laboratory Investigation

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Currently, no suitable biomarker for the early detection or follow-up of renal cell carcinoma (RCC) is available. We aimed to validate previously reported potential serum biomarkers for RCC obtained with Surface Enhanced Laser Desorption Ionisation-Time of Flight Mass Spectrometry (SELDI-TOF MS) in our laboratory using distinct patient populations. Two sets of sera from RCC patients and healthy controls (HC) were gathered from different institutes and analysed according to published procedures. The first set (40 RCC, 32 HC) consisted of mainly presurgery samples from patients with disease stages I-IV. The second set (26 RCC, 27 HC) were mostly sera from patients with stage-IV disease, drawn after nephrectomy. Only the increased expression of the previously found serum amyloid-a (SAA) peak cluster could be validated in a similar RCC patient subset in both our populations in two independent analyses. It was seen both in earlyand late-stage disease and in pre-and postsurgery samples. These results were also confirmed by ELISA. Other previously identified biomarker candidates (mass-to-charge ratio's (m/z) 3900, 4107, 4153, 5352 and 5987) proved difficult to reproduce upon duplicate analysis. Modification of the analytical protocol for these markers resulted in their detection, but we did not achieve satisfactory classification of patients and controls with these alleged biomarkers in any of our two sample sets. Instead, two new peaks (m/z 4289 and 8151) were identified with better performance (sensitivity and specificity B65-90%) for separating patients from controls in the first sample set. Concluding, only the SAA peak cluster was validated as a robust RCC biomarker candidate, which is present in a specific subset of these patients, regardless of disease stage or nephrectomy status. In addition, two new peaks were seen which might prove useful as biomarkers, provided these are validated in new populations. Renal cell carcinoma (RCC) is difficult to diagnose at early stages due to a lack of clear clinical symptoms. When symptoms do occur, about 30% of patients already have metastatic disease. In addition, a similar part of patients with resection of localised disease will have a recurrence. 1 Therefore, a need remains for reliable markers for diagnosis and follow-up of RCC, preferably in easy-accessible body fluids. Surface Enhanced Laser Desorption Ionisation-Time of Flight Mass Spectrometry (SELDI-TOF MS) 2,3 is being increasingly used to search for new and better tumour markers in (serum) protein profiles, for example, for ovarian, 4 breast, 5 prostate 6 and colorectal cancer. 7 Its appeal lies in the ease with which a multitude of samples can be analysed with a minimum of sample preparation in a single SELDI-TOF MS analysis. Indeed, SELDI-TOF MS has also been performed to identify biomarker proteins for early detection of RCC. Two studies describe protein profiling of serum with SELDI-TOF MS. 8,9 Tolson et al 8 reported a peak cluster at a mass-to-charge ratio (m/z) of approximately 11 000 from serum amyloid a-...

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confidence: 99%

Validation of SELDI-TOF MS serum protein profiles for renal cell carcinoma in new populations

Engwegen

Mehra

Haanen

et al. 2007

Laboratory Investigation

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“…[9][10][11][12][13][15][16][17][18][19][20][21]25 The most interesting discovery of the study was the finding that a SELDI-derived peak (m/z 4,462) was as effective at discriminating cancer from benign serum as the tumor markers CEA or CA19.9, while combining these three serum markers marginally improved classification. Classification could be further improved with data generated from a panel of peaks, suggesting analysis of proteomic profiles, rather than individual proteins, may yield improved diagnostic ability.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13][15][16][17][18][19][20][21]25 A potential source of error in the tissue group not present in the serum study may be sampling error. The high desmoplastic nature of CCs means the sampled tissue may miss the malignant portion of the tumor and may mainly consist of stroma rather than cholangiocytes proper.…”

Section: Discussionmentioning

confidence: 99%

“…Proteomic profiling of serum has been used with a number of other malignancies to discover potential biomarkers. 7,8 In particular, affinity-based arrays-such as the protein chips analyzed via surface-enhanced laser desorption/ionization time-offlight mass spectrometry (SELDI-TOF MS) used in this study-have been used to successfully identify malignant patterns in serum from ovarian, [9][10][11] pancreatic, [12][13][14] head and neck, 15,16 prostate, 17 transitional cell, 18 renal cell, 19,20 and breast 21 cancers. TOF-MS separates ions derived from proteins or protein fragments that are differentially detected according to their mass-to-charge ratio.…”

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confidence: 99%

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Proteomic profiling of cholangiocarcinoma: Diagnostic potential of SELDI-TOF MS in malignant bile duct stricture

et al. 2006

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Proteomic techniques promise to improve the diagnosis of cholangiocarcinoma (CC) in both tissue and serum as histological diagnosis and existing serum markers exhibit poor sensitivities. We explored the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify potential protein biomarkers of CC. Twenty-two resected CC samples were compared with adjacent noninvolved bile duct tissue. Serum from patients with CC (n ‫؍‬ 20) was compared with patients with benign disease (n ‫؍‬ 20), and healthy volunteers (n ‫؍‬ 25). Samples were analyzed on hydrophobic protein chips via SELDI-TOF MS, and classification models were developed using logistic regression and cross-validation analysis. Univariate analysis revealed 14 individual peaks differentially expressed between CC and bile duct tissue, 4 peaks between CC and benign disease, and 12 peaks between CC and sera of healthy volunteers. The 4,462 mass-to-charge serum peak had superior discriminatory ability to carbohydrate antigen 19.9 (CA19.9) and carcinoembryonic antigen ( C holangiocarcinoma (CC) is a rare but devastating neoplasm that accounts for 3% of all gastrointestinal cancers and 15% of all primary liver cancers worldwide. 1 Five thousand new cases are diagnosed on average per year in the United States, and the incidence is rising. 2 Northeast Thailand sees the highest incidence, with 96 cases per 100,000. 1 Surgical resection is the only current chance of cure, with no proven adjunctive therapy; however, this approach has a mortality rate of 5% to 10%. 3 Even with margin-free resection, 5-year survival figures only reach 20% to 40%. 3,4 Unresectable disease is usually fatal within 6 months to 1 year, and over one third of patients present at a stage too late for resection. 3 This confirms the need for earlier and more accurate diagnostic processes.At present, diagnosis of CC relies on imaging of the biliary tree with computed tomography or ultrasonography in the presence of high clinical suspicion. Tissue diagnostic confirmation is possible for intrahepatic tumors but is very difficult in more distal and more common (2/3 of cases) extrahepatic cases. These frequently present as a stricture of the common bile duct, which can be further characterized by means of endoscopic retrograde cholangio-pancreatography. 5

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“…These techniques can also be used to identify specific CSF biomarkers of CNS diseases that could be used for their detection, diagnosis, and monitoring [11][12][13][14]. 2-DE has been the gold standard for protein separation, and its combination with MS has led to the identification of numerous proteins within the normal CSF as well as potential protein markers for neurodegenerative diseases, demyelinating diseases, Creutzfeld Jacob Disease (CJD), primary CNS neoplasms, and other neurologic disorders [15,16].…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of cerebrospinal fluid discriminates malignant and nonmalignant disease of the central nervous system and identifies specific protein markers

et al. 2006

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CNS diseases are often accompanied by changes in the protein composition of cerebrospinal fluid (CSF). SELDI-TOF-MS provides an approach for identifying specific protein markers of disease in biological fluids. We compared the CSF proteomes from patients with neoplastic and reactive/inflammatory CNS diseases to identify potential biomarkers. SELDI-TOF-MS was performed on CSF derived from lumbar puncture of 32 patients, including 10 with CNS malignancies, 12 with inflammatory or reactive conditions, and 10 with unknown CNS disease. Using the SAX-2 (strong anionic exchange) chip, we uncovered three conserved protein peak ranges within each disease category. For neoplastic diseases, we identified conserved peaks at 7.5-8.0 kDa (9/10 samples), 15.1-15.9 kDa (8/10 samples), and 30.0-32.0 kDa (5/10 samples). In reactive/inflammatory diseases, conserved peaks were found at 6.7-7.1 kDa (10/12 samples), 11.5-11.9 kDa (12/12 samples), and 13.3-13.7 kDa (9/12 samples). A protein from the 30.0 to 32.0 kDa peak range found in neoplastic CSF was identified by MALDI analysis as carbonic anhydrase, a protein overexpressed in many malignancies including high-grade gliomas. Similarly, cystatin C was identified in the 13.3-13.7 kDa peak range in non-neoplastic CSF and was most prominent in inflammatory conditions. Our approach provides a rational basis for identifying biomarkers that could be used for detection, diagnosis, and monitoring of CNS diseases.

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Pattern analysis of serum proteome distinguishes renal cell carcinoma from other urologic diseases and healthy persons

Cited by 103 publications

References 10 publications

Validation of SELDI-TOF MS serum protein profiles for renal cell carcinoma in new populations

Validation of SELDI-TOF MS serum protein profiles for renal cell carcinoma in new populations

Proteomic profiling of cholangiocarcinoma: Diagnostic potential of SELDI-TOF MS in malignant bile duct stricture

Proteomic analysis of cerebrospinal fluid discriminates malignant and nonmalignant disease of the central nervous system and identifies specific protein markers

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