Differential Capture of Serum Proteins for Expression Profiling and Biomarker Discovery in Pre‐ and Posttreatment Head and Neck Cancer Samples

Freed, Gary L.; Cazares, Lisa H.; Fichandler, Craig E.; Fuller, Thomas W.; Sawyer, Christopher; Stack, Brendan C.; Schraff, Scott A.; Semmes, O. John; Wadsworth, J. Trad; Drake, Richard

doi:10.1097/mlg.0b013e31814cf389

Cited by 64 publications

(37 citation statements)

References 32 publications

(63 reference statements)

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“…In most recent proteomics studies done on HNSCC cell lines, tissues, saliva, and secretomes aiming at biomarker discovery for head and neck cancer, normal samples and precancerous tissue (when used) are usually defined by abnormal histology (31)(32)(33)(34)(35)(36)(37)(38)(39). To our knowledge, our study is the first to use detailed genetic characterizations to ascertain the selection of strictly normal and precancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

Schaaij-Visser

Graveland

Gauci

et al. 2009

Clinical Cancer Research

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Purpose: The 5-year survival rates of head and neck squamous cell carcinomas (HNSCC) remain disappointing. HNSCCs develop in precursor fields of genetically altered cells that are often not completely resected when the tumor is excised, causing local relapse. These precursor fields are mostly recognized as dysplasia, but histologic grading cannot reliably predict malignant transformation. Our aim was to discover and validate protein biomarkers that can detect precursor fields and predict local relapse in HNSCC using immunostaining of surgical margins. Experimental Design: We compared paired and genetically characterized normal, precursor, and tumor tissues of eight patients by proteome analysis to identify differentially expressed proteins. The prognostic value of candidate protein biomarkers was evaluated by immunohistochemical analysis of 222 surgical margins of 46 HNSCC patients who developed local relapse or remained disease free. Significant associations were determined by Kaplan-Meier survival analysis and Cox-proportional hazards models. Results: Forty proteins showed significant differential expression (false discovery ratecorrected P < 0.05). Most discriminative markers suited for immunostaining were keratin 4 and cornulin. Low expression in the surgical margins of keratin 4 (hazard ratio, 3.8; P = 0.002), cornulin (hazard ratio, 2.7; P = 0.025), and their combination (hazard ratio, 8.8; P = 0.0005) showed a highly significant association with the development of local relapse. Dysplasia grading had no prognostic relevance. Conclusions: Immunohistochemical assessment of keratin 4 and cornulin expression in surgical margins of HNSCC patients outperforms histopathologic grading in predicting the risk for local relapse. These markers can be used to initiate more frequent and lifelong surveillance of patients at high risk of local relapse, and enable selection for adjuvant treatment or tertiary prevention trials. (Clin Cancer Res 2009;15(24):7666-75) Head and neck squamous cell carcinoma (HNSCC) develops in the mucosal linings of the upper aerodigestive tract and is the sixth most common cancer worldwide (1). The 5-year survival rates of HNSCC are approximately 60% (1) and have only moderately improved the last decades (2) mainly because 20% to 40% of all patients develop a local relapse in the same or adjacent anatomic region even when the surgical margins are histologically tumor free (3, 4). Clinically these relapses at the primary and adjacent anatomic sites are assigned as local recurrences when they develop within three years and at <2 cm distance of the primary tumor. Relapses not fulfilling these criteria are clinically classified as second primary tumors. Despite the difference in clinical assignment, many local relapses have in fact the same pathobiological origin (3-8).It has been well established that HNSCC is the result of a multistep process characterized by the accumulation of genetic and epigenetic alterations (9). Genetic analysis of surgical margins has shown that HNSCC frequent...

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Section: Discussionmentioning

confidence: 99%

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

Schaaij-Visser

Graveland

Gauci

et al. 2009

Clinical Cancer Research

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“…Other methods based on the biological fl uid proteome prefractionation have been recently made available (11,12). The successful discovery of a proteomic profi le correlated to an altered state by the ClinProt method has been reported in various human diseases, such as oral, bladder, nasopharyngeal and neck cancer (13)(14)(15). Recently, we have used this approach to fi nd possible ccRCC biomarkers in urine and serum (12,16).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

Ornellas¹,

Ornellas²,

Chinello³

et al. 2012

Int. braz j urol.

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Purpose: To investigate the use of ClinProt technique to identify cancer markers in plasma of patients suffering from squamous cell carcinoma of the penis (SCCP). Materials and Methods: Plasma of 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment between June 2010 and June 2011 was collected and analyzed by the ClinProt/MALDI/ToF technique. Then the peptides were identifi ed from the C8 MB eluted fraction of patients' and control subjects' plasma by LIFT MS/MS. Results: A cluster of 2 peptides (A=m/z 1897.22 ± 9 Da and B=m/z 2021.99 ± 9 Da) was able to discriminate patients from control subjects. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% sensitivity and specifi city, respectively. The cluster also showed very high sensitivity (100%) and specifi city (97%) for SCCP patients that died due to the disease. Furthermore, patients with lymph node involvement presented sensitivity and specifi city of 80% and 97%, respectively. These two peptides were identifi ed by the proteomic approach based on a MALDI-TOF/TOF as fragments of C3 (m/z 1896.17) and C4a/b (m/z 2021.26) complement proteins. Conclusions:The results showed that as the disease progresses, the fragments C3 and C4 A/B are less expressed in comparison with healthy subjects. These results may be useful as prognostic tools.

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“…So far, to overcome this issue, an adequate fractionation step prior proteomic analysis is mandatory in order to remove high-abundant components. Several prefractionation methodologies have been introduced such as ultracentrifugation [4,16], solid-phase extraction (SPE) columns [17][18][19][20][21], size fractionation [22], derivatized beads [23,24], combinatorial peptide ligand libraries [25], and specific enrichment techniques [26][27][28][29]. Moreover, the high cost, the scarce selectivity, or long operation times, impose the development of new depletion systems based on multiple affinity columns [30,31].…”

Section: Introductionmentioning

confidence: 99%

Setup for human sera MALDI profiling: The case of rhEPO treatment

et al. 2011

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The implementation of high-throughput technologies based on qualitative and quantitative methodologies for the characterization of complex protein mixtures is increasingly required in clinical laboratories. MALDI profiling is a robust and sensitive technology although the serum high dynamic range imposes a major limitation hampering the identification of less abundant species decreasing the quality of MALDI profiling. A setup to improve these parameters has been performed for recombinant human erythropoietin (rhEPO) monitoring in serum, analyzing the effects of two commercially available columns (MARS Hu7 and Hu14) for immunodepletion, and two matrices (acyano-4-hydroxycinnamic acid and 2 0 ,4 0 -dihydroxyacetophenone) for peak quality improvement. The immunodepletion capability of both columns was determined by 2-D DIGE, which precisely revealed the efficacy of Hu14 in protein removal and the serum dynamic range decrement. In addition, the type of matrix, the sample dilution, and the efficacy of optimized parameters were used for serum profiling of ten healthy subjects before and after rhEPO treatment. The principal component analysis indicates that a combination of Hu14 column and 2 0 ,4 0 -dihydroxyacetophenone matrix increases data quality allowing the discrimination between treated and untreated samples, making serum MALDI profiling suitable for clinical monitoring of rhEPO.

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Differential Capture of Serum Proteins for Expression Profiling and Biomarker Discovery in Pre‐ and Posttreatment Head and Neck Cancer Samples

Cited by 64 publications

References 32 publications

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

Setup for human sera MALDI profiling: The case of rhEPO treatment

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