Serum Protein Profile Alterations in Hemodialysis Patients

Langlois, Richard G.; Trebes, J. E.; Dalmasso, Enrique A.; Ying, Yun; Davies, Robert W.; Curzi, Mario P.; Colston, Bill W.; Turteltaub, Kenneth W.; Perkins, Julie; Chromy, Brett A.; Choi, Megan; Murphy, Gloria A.; Fitch, J. Patrick; McCutchen-Maloney, Sandra L.

doi:10.1159/000077409

Cited by 25 publications

(21 citation statements)

References 17 publications

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“…Despite that we found some other expression differences in both sample sets, these were not large enough for good classification of patients and controls. Furthermore, both a decrease of a 17.3-kDa peak (possibly des-glutamine apolipoprotein A-II) and glutathionylated transthyretin have been described in the sera from patients with other cancers before 24,[28][29][30] and thus they seem not specific for RCC either. Yet, these proteins might have a role as markers in disease or therapy monitoring.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The small, dense LDLs of diabetes patients were found enriched in apo C-III and depleted of apo C-I, apo A-I, and apo E compared with matched healthy controls [261]. Serum proteomic pattern analysis could be used for evaluation of periodic hemodialysis treatment [262] and for assessment of the remission from active Wegener's granulomatosis [263]. Based on a 2-DE/Western blotting approach, ~85 immunoreactive protein species were detected with systemic candidiasis patients' serum specimens.…”

Section: Application To Human Disease Detectionmentioning

confidence: 99%

Human body fluid proteome analysis

2006

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The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.

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“…M/z 2743 has been previously found to be decreased in serum of patients with renal failure undergoing haemodialysis (44). We propose fetuin A as this protein's identity.…”

Section: Discussionmentioning

confidence: 59%

Identification of two new serum protein profiles for renal cell carcinoma

Engwegen

Mehra²,

Haanen³

et al. 2009

Oncol Rep

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Abstract. Renal cell carcinoma (RCC) is the most lethal urological cancer, and survival greatly depends on early diagnosis. Therefore, reliable, new biomarkers for detection of RCC are required. We assessed serum protein profiles of samples from two institutes with SELDI-TOF MS in duplicate on CM10 chips at pH 6.0 (set 1: 37 RCC + 32 healthy controls (HC), set 2: 20 RCC + 25 HC). Mean peak intensities of detected proteins were compared between RCC and HC with non-parametric testing. Classification trees were built with discriminating peaks using one sample set as training set and the other as independent validation set. We found 15 peaks significantly different (p<0.01) between RCC and HC. Two classification trees could be built with these peaks. Tree A achieved 75% sensitivity and 85% specificity for crossvalidation and 76 and 65% for independent validation. Tree B had 71 and 62% sensitivity and specificity for cross-validation and 83 and 82% for independent validation. Although two serum protein profiles comprising 5 protein peaks were found that could separate RCC from HC, the sensitivity and specificity is not sufficient to recommend large scale use. Upon structural identification and quantitative validation, however, these proteins might prove suitable markers in the follow up of RCC patients.

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Serum Protein Profile Alterations in Hemodialysis Patients

Cited by 25 publications

References 17 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

Human body fluid proteome analysis

Identification of two new serum protein profiles for renal cell carcinoma

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