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Prognostic value of DLGAP5 in colorectal cancer

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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.

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Acknowledgments

This study was initially supervised by our friend and mentor Prof. Moritz Koch, who passed away in 2015. This paper is dedicated to his memory.

The authors thank Melanie Bernhard, Maria Thomalla-Starzl, and Marzena Knyssok-Sypniewski for outstanding technical assistance.

Author contribution list

  1. 1.

    Vittorio Branchi: study design and supervision, data collection, statistical analysis, data interpretation, drafting of the manuscript

  2. 2.

    Sebastian Garcia: data collection, statistical analysis, data interpretation, critical revision of the manuscript

  3. 3.

    Praveen Radhakrishnan: data interpretation, critical revision of the manuscript

  4. 4.

    Balázs Győrffy: statistical analysis, critical revision of the manuscript

  5. 5.

    Barbara Hissa: data interpretation, critical revision of the manuscript

  6. 6.

    Martin Schneider: data interpretation, critical revision of the manuscript

  7. 7.

    Christoph Reissfelder: data interpretation, critical revision of the manuscript

  8. 8.

    Sebastian Schölch: study design and supervision, statistical analysis, data interpretation, drafting of the manuscript

Funding

This work was funded by the KFO 227 program (Clinical Research Group 227: Colorectal cancer: from primary tumor progression towards metastases (WE 3548/4–1/2) of Deutsche Forschungsgemeinschaft (DFG).

Author information

Authors and Affiliations

  1. Department of General, Abdominal, Thoracic and Vascular Surgery, Medical Faculty Bonn, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Vittorio Branchi

  2. Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany

    Sebastián A. García

  3. Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Heidelberg, Kirschnerstr. 1, 69120, Heidelberg, Germany

    Praveen Radhakrishnan & Martin Schneider

  4. 2nd Department of Pediatrics, Semmelweis University, Tűzoltó u. 7-9, Budapest, H-1094, Hungary

    Balázs Győrffy

  5. MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary

    Balázs Győrffy

  6. Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany

    Barbara Hissa, Christoph Reißfelder & Sebastian Schölch

  7. German Cancer Consortium (DKTK), Heidelberg, Germany

    Martin Schneider, Christoph Reißfelder & Sebastian Schölch

  8. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Martin Schneider, Christoph Reißfelder & Sebastian Schölch

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  1. Vittorio Branchi
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  3. Praveen Radhakrishnan
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  8. Sebastian Schölch
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Correspondence to Sebastian Schölch.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (ethics committee of the University of Heidelberg, ethics committee number 323/2004) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent was obtained from all individual participants included in the study.

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Branchi, V., García, S.A., Radhakrishnan, P. et al. Prognostic value of DLGAP5 in colorectal cancer. Int J Colorectal Dis 34, 1455–1465 (2019). https://doi.org/10.1007/s00384-019-03339-6

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