Jaco C Knol1, Meike de Wit1, Jakob Albrethsen2, Sander R Piersma1, Thang V Pham1, Sandra Mongera3, Beatriz Carvalho3, Remond J A Fijneman3, Gerrit A Meijer3, Connie R Jiménez4. 1. OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. 2. OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands; Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark. 3. Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. 4. OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: c.jimenez@vumc.nl.
Abstract
BACKGROUND: Altered nuclear and genomic structure and function are hallmarks of cancer cells. Research into nuclear proteins in human tissues could uncover novel molecular processes in cancer. Here, we examine biochemical tissue fractions containing chromatin-binding (CB) proteins in the context of colorectal cancer (CRC) progression. METHODS: CB protein-containing fractions were biochemically extracted from human colorectal tissues, including carcinomas with chromosomal instability (CIN), carcinomas with microsatellite instability (MIN), and adenomas. The CB proteins were subjected to label-free LC-MS/MS and the data were analyzed by bioinformatics. RESULTS: Over 1700 proteins were identified in the CB fraction from colonic tissues, including 938 proteins associated with nuclear annotation. Of the latter, 169 proteins were differential between adenomas and carcinomas. In this adenoma-versus-carcinoma comparison, apart from specific changes in components of the splicing and protein translational machineries, we also identified significant changes in several proteins associated with chromatin-directed functions. Furthermore, several key cell cycle proteins as well as those involved in cellular stress were increased, whereas specific components of chromosome segregation and DNA recombination/repair systems were decreased. CONCLUSIONS: Our study identifies proteomic changes at the subnuclear level that are associated with CRC and may be further investigated. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
BACKGROUND: Altered nuclear and genomic structure and function are hallmarks of cancer cells. Research into nuclear proteins in human tissues could uncover novel molecular processes in cancer. Here, we examine biochemical tissue fractions containing chromatin-binding (CB) proteins in the context of colorectal cancer (CRC) progression. METHODS: CB protein-containing fractions were biochemically extracted from human colorectal tissues, including carcinomas with chromosomal instability (CIN), carcinomas with microsatellite instability (MIN), and adenomas. The CB proteins were subjected to label-free LC-MS/MS and the data were analyzed by bioinformatics. RESULTS: Over 1700 proteins were identified in the CB fraction from colonic tissues, including 938 proteins associated with nuclear annotation. Of the latter, 169 proteins were differential between adenomas and carcinomas. In this adenoma-versus-carcinoma comparison, apart from specific changes in components of the splicing and protein translational machineries, we also identified significant changes in several proteins associated with chromatin-directed functions. Furthermore, several key cell cycle proteins as well as those involved in cellular stress were increased, whereas specific components of chromosome segregation and DNA recombination/repair systems were decreased. CONCLUSIONS: Our study identifies proteomic changes at the subnuclear level that are associated with CRC and may be further investigated. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.