Colon cancer : disease related proteins in tumor tissue and serum
Author: Roblick, Uwe Johannes
Date: 2004-12-10
Location: Föreläsningssalen, Medicinhistoriska Museet
Time: 9.00
Department: Institutionen för onkologi-patologi / Department of Oncology-Pathology
Abstract
Despite the progress in surgical techniques and adjuvant therapies the
mortality of around 60% within the group of colon cancer patients did not
decrease significantly over the last decades. This determines a growing
demand for biomarkers for early detection, prognosis and risk assessment
in colorectal malignancies. Desirable criteria for such a biomarker test
are minimal burden and maximum safety for the patient, cost efficiency
and broad acceptance to reach a high compliance of the patients.
More than 300 colon tissue samples and 1000 sera were obtained from CRC and FAP patients at the Lübeck and Düsseldorf University Hospitals in Germany. To identify the consequences of genetic aberrations on protein expression level, samples from patients with advanced sporadic colon cancers in which the corresponding mucosa, adenoma, carcinoma and liver metastasis were available, were analyzed by 2-D gel electrophoresis and mass spectrometry. A total of 46 proteins were found to be upregulated during the progression of sporadic cancer, and 26 were downregulated. Several of the identified polypeptides correlate with proteins regulating specific cell functions (cell cycle, cytoskeleton, metabolic pathways).
In a further study we used a 2-DE based proteomic approach to compare the expression pattern of normal colonic mucosa vs. mucosa gained from FAP patients, polyps vs. FAP polyps and sporadic vs. FAP associated cancer, respectively. A total of 47 proteins were always present in FAP mucosa and absent in the normal mucosa. Based on a total of 37 proteins FAP polyps and sporadic polyps could be distinctly separated. In addition, the absence/presence pattern of 66 spots allowed to distinguish FAP cancers from sporadic cancers. These data suggest, that proteome analysis makes it possible to diagnose FAP already on macroscopically normal appearing colonic mucosa. By means of SELDI array based investigations we unrevealed 16 serum proteins that were able to classify 98% of all test set samples correctly. Our SELDI results show that serum marker protein profiling enables to diagnose and discern malignant colon cancer patients from healthy individuals. Although these markers need validation before they can be used in clinics they have potential for the design of a marker panel for objective diagnosis and therapeutic strategies for colorectal cancer and metastasis.
More than 300 colon tissue samples and 1000 sera were obtained from CRC and FAP patients at the Lübeck and Düsseldorf University Hospitals in Germany. To identify the consequences of genetic aberrations on protein expression level, samples from patients with advanced sporadic colon cancers in which the corresponding mucosa, adenoma, carcinoma and liver metastasis were available, were analyzed by 2-D gel electrophoresis and mass spectrometry. A total of 46 proteins were found to be upregulated during the progression of sporadic cancer, and 26 were downregulated. Several of the identified polypeptides correlate with proteins regulating specific cell functions (cell cycle, cytoskeleton, metabolic pathways).
In a further study we used a 2-DE based proteomic approach to compare the expression pattern of normal colonic mucosa vs. mucosa gained from FAP patients, polyps vs. FAP polyps and sporadic vs. FAP associated cancer, respectively. A total of 47 proteins were always present in FAP mucosa and absent in the normal mucosa. Based on a total of 37 proteins FAP polyps and sporadic polyps could be distinctly separated. In addition, the absence/presence pattern of 66 spots allowed to distinguish FAP cancers from sporadic cancers. These data suggest, that proteome analysis makes it possible to diagnose FAP already on macroscopically normal appearing colonic mucosa. By means of SELDI array based investigations we unrevealed 16 serum proteins that were able to classify 98% of all test set samples correctly. Our SELDI results show that serum marker protein profiling enables to diagnose and discern malignant colon cancer patients from healthy individuals. Although these markers need validation before they can be used in clinics they have potential for the design of a marker panel for objective diagnosis and therapeutic strategies for colorectal cancer and metastasis.
List of papers:
I. Lenander C, Roblick UJ, Habermann JK, Ost A, Tryggvason K, Auer G (2003). "Laminin 5 gamma 2 chain expression: a marker of early invasiveness in colorectal adenomas. " Mol Pathol 56(6): 342-6
Pubmed
II. Roblick UJ, Hirschberg D, Habermann JK, Palmberg C, Becker S, Kruger S, Gustafsson M, Bruch HP, Franzen B, Ried T, Bergmann T, Auer G, Jornvall H (2004). "Sequential proteome alterations during genesis and progression of colon cancer." Cell Mol Life Sci 61(10): 1246-55
Pubmed
III. Roblick UJ, Habermann JK, Lenander C, Zimmermann K, Becker S, Kruger S, Bruch HP, Franzen B, Ried T, Schimmelpenning H, Auer G (2004). "Cancer proteomics - A valid tool for diagnosing pelvic adenocarcinomas with unclear origin." (Submitted)
View record in Web of Science®
IV. Roblick UJ, Unger A, Ploner A, Habermann JK, Hirschberg D, Zimmermann K, Becker S, Moeslein G, Bruch HP, Franzen B, Ried T, Schimmelpenning H, Jornvall H, Auer G (2004). "Protein expression in human sporadic and hereditary colon cancer - a proteomics based comparison." (Manuscript)
V. Schiedeck TH, Wellm C, Roblick UJ, Broll R, Bruch HP (2003). "Diagnosis and monitoring of colorectal cancer by L6 blood serum polymerase chain reaction is superior to carcinoembryonic antigen-enzyme-linked immunosorbent assay. " Dis Colon Rectum 46(6): 818-25
Pubmed
VI. Roblick UJ, Habermann JK, Luke B, Prieto DaRue, Oevermann E, Moeslein G, Schiedeck THK, Veenstra TD, Burt SK, Bruch HP, Franzen B, Auer G, Ried T (2004). "Detection of colorectal cancer by serum protein profiling." (Manuscript)
I. Lenander C, Roblick UJ, Habermann JK, Ost A, Tryggvason K, Auer G (2003). "Laminin 5 gamma 2 chain expression: a marker of early invasiveness in colorectal adenomas. " Mol Pathol 56(6): 342-6
Pubmed
II. Roblick UJ, Hirschberg D, Habermann JK, Palmberg C, Becker S, Kruger S, Gustafsson M, Bruch HP, Franzen B, Ried T, Bergmann T, Auer G, Jornvall H (2004). "Sequential proteome alterations during genesis and progression of colon cancer." Cell Mol Life Sci 61(10): 1246-55
Pubmed
III. Roblick UJ, Habermann JK, Lenander C, Zimmermann K, Becker S, Kruger S, Bruch HP, Franzen B, Ried T, Schimmelpenning H, Auer G (2004). "Cancer proteomics - A valid tool for diagnosing pelvic adenocarcinomas with unclear origin." (Submitted)
View record in Web of Science®
IV. Roblick UJ, Unger A, Ploner A, Habermann JK, Hirschberg D, Zimmermann K, Becker S, Moeslein G, Bruch HP, Franzen B, Ried T, Schimmelpenning H, Jornvall H, Auer G (2004). "Protein expression in human sporadic and hereditary colon cancer - a proteomics based comparison." (Manuscript)
V. Schiedeck TH, Wellm C, Roblick UJ, Broll R, Bruch HP (2003). "Diagnosis and monitoring of colorectal cancer by L6 blood serum polymerase chain reaction is superior to carcinoembryonic antigen-enzyme-linked immunosorbent assay. " Dis Colon Rectum 46(6): 818-25
Pubmed
VI. Roblick UJ, Habermann JK, Luke B, Prieto DaRue, Oevermann E, Moeslein G, Schiedeck THK, Veenstra TD, Burt SK, Bruch HP, Franzen B, Auer G, Ried T (2004). "Detection of colorectal cancer by serum protein profiling." (Manuscript)
Issue date: 2004-11-19
Publication year: 2004
ISBN: 91-7140-171-7
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