Vittorio Branchi1, Sebastián A García2, Praveen Radhakrishnan3, Balázs Győrffy4,5, Barbara Hissa6, Martin Schneider3,7,8, Christoph Reißfelder6,7,8, Sebastian Schölch9,10,11. 1. Department of General, Abdominal, Thoracic and Vascular Surgery, Medical Faculty Bonn, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. 2. Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany. 3. Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Heidelberg, Kirschnerstr. 1, 69120, Heidelberg, Germany. 4. 2nd Department of Pediatrics, Semmelweis University, Tűzoltó u. 7-9, Budapest, H-1094, Hungary. 5. MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary. 6. Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany. 7. German Cancer Consortium (DKTK), Heidelberg, Germany. 8. German Cancer Research Center (DKFZ), Heidelberg, Germany. 9. Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany. sebastian.schoelch@umm.de. 10. German Cancer Consortium (DKTK), Heidelberg, Germany. sebastian.schoelch@umm.de. 11. German Cancer Research Center (DKFZ), Heidelberg, Germany. sebastian.schoelch@umm.de.
Abstract
PURPOSE: DLG7 (disc large homolog 7) is a microtubule-associated protein encoded by DLGAP5 (DLG associated protein 5) gene and has an important role during spindle assembly. Spindle assembly deregulation is a well-known cause of genomic instability. The aim of this study was to investigate the influence of DLGAP5 expression on survival and to evaluate its potential use as a biomarker in colorectal cancer (CRC). METHODS: DLGAP5 expression was measured in the primary tumor and corresponding normal mucosa samples from 109 patients with CRC and correlated to clinical and pathological data. The results were validated in a second, publically available patient cohort. Molecular effects of DLG7/DLGAP5 in CRC were analyzed via functional assays in knockdown cell lines. RESULTS: DLGAP5 downregulation led to a significant reduction of the invasion and migration potential in CRC. In addition, DLGAP5 expression correlates with nodal status and advanced UICC stage (III-IV).Subgroup analyses revealed a correlation between DLGAP5 overexpression and poor survival in patients with non-metastatic disease (M0). Furthermore, overexpression of DLGAP5 is associated with worse overall survival in distinct molecular CRC subtypes. CONCLUSIONS: The results of this study suggest the importance of DLGAP5 in defining a more aggressive CRC phenotype. DLG7/DLGAP5 represents a potential biomarker for CRC in molecular subgroups of CRC.
PURPOSE:DLG7 (disc large homolog 7) is a microtubule-associated protein encoded by DLGAP5 (DLG associated protein 5) gene and has an important role during spindle assembly. Spindle assembly deregulation is a well-known cause of genomic instability. The aim of this study was to investigate the influence of DLGAP5 expression on survival and to evaluate its potential use as a biomarker in colorectal cancer (CRC). METHODS:DLGAP5 expression was measured in the primary tumor and corresponding normal mucosa samples from 109 patients with CRC and correlated to clinical and pathological data. The results were validated in a second, publically available patient cohort. Molecular effects of DLG7/DLGAP5 in CRC were analyzed via functional assays in knockdown cell lines. RESULTS:DLGAP5 downregulation led to a significant reduction of the invasion and migration potential in CRC. In addition, DLGAP5 expression correlates with nodal status and advanced UICC stage (III-IV).Subgroup analyses revealed a correlation between DLGAP5 overexpression and poor survival in patients with non-metastatic disease (M0). Furthermore, overexpression of DLGAP5 is associated with worse overall survival in distinct molecular CRC subtypes. CONCLUSIONS: The results of this study suggest the importance of DLGAP5 in defining a more aggressive CRC phenotype. DLG7/DLGAP5 represents a potential biomarker for CRC in molecular subgroups of CRC.
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