Prognostic value of DLGAP5 in colorectal cancer

Vittorio Branchi, Sebastián A. García, Praveen Radhakrishnan, B. Györffy, Barbara Hissa, Martin Schneider, Christoph Reißfelder, Sebastian Schölch

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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.

Original languageEnglish
Pages (from-to)1455-1465
Number of pages11
JournalInternational Journal of Colorectal Disease
Volume34
Issue number8
DOIs
Publication statusPublished - Aug 1 2019

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Keywords

  • Colorectal cancer
  • DLG7
  • DLGAP5
  • Metastasis
  • Survival

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Branchi, V., García, S. A., Radhakrishnan, P., Györffy, B., Hissa, B., Schneider, M., Reißfelder, C., & Schölch, S. (2019). Prognostic value of DLGAP5 in colorectal cancer. International Journal of Colorectal Disease, 34(8), 1455-1465. https://doi.org/10.1007/s00384-019-03339-6