Expression of the EGFR-RAS Inhibitory Proteins DOK1 and MTMR7 and its Significance in Colorectal Adenoma and Adenoma Recurrence

Authors

  • Tobias Gutting Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg; 2) Department of Internal Medicine IV, University Hospital Heidelberg, Germany
  • Andreas Merkel Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Germany
  • David J Fink Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Germany
  • Svetlana Hetjens Department of Medical Statistics, Medical Faculty Mannheim, University of Heidelberg, Germany
  • Philip Weidner Department of Medicine II, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg
  • Yanxiong Yu Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Germany
  • Georg Kähler Central Interdisciplinary Endoscopy, Medical Faculty Mannheim, University of Heidelberg, Germany
  • Matthias P. Ebert Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Germany
  • Timo Gaiser Institute of Pathology, Medical Faculty Mannheim, University of Heidelberg, Germany
  • Elke Burgermeister Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg, Germany
  • Sebastian Belle Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg; Central Interdisciplinary Endoscopy, Medical Faculty Mannheim, University of Heidelberg, Germany

DOI:

https://doi.org/10.15403/jgld-3681

Keywords:

colorectal adenoma, adenoma recurrence, DOK1, MTMR7, serrated adenoma

Abstract

Background and Aims: Colorectal adenomas are precursor lesions for colorectal cancer (CRC), a major cause of cancer-related death. Despite all molecular insights, there are still unknown variables in the development of CRC as well as uncertainties regarding adenoma recurrence after resection. We aimed to characterize the expression of docking protein 1 (DOK1) and myotubularin-related protein 7 (MTMR7), which share inhibiting functions on EGFR-RAS-signalling, a major oncogenic driver in CRC, and their association with clinical variables and adenoma recurrence.

Methods: This observational study is based on clinical data obtained from patients who underwent routine endoscopy and consecutive follow-up examinations. Immunohistochemistry was conducted both in dysplastic tissue and adjacent non-dysplastic mucosa followed by microscopical assessment. Recurrence was differentiated between local, segmental and distant relapse.

Results: A total of 56 patients (23 females) gathering 96 adenomas/polyps were included. 36 patients experienced a metachronous lesion, 23 patients had simultaneous lesions in their index endoscopy. Female patients showed lower levels of MTMR7 in adenomas (p=0.0318). Adenomas of young patients showed lower DOK1 than those of older patients (p=0.0469). Big adenomas showed a higher expression of DOK1 than small lesions (p=0.0044). In serrated lesions, DOK1 was reduced (p=0.0026) and correlated with the quantity of lesions (p < 0.001). MTMR7 was significantly reduced in distant (p=0.05) and local segmental recurrence (p=0.0362), while DOK1 showed higher expression in recurrence (p=0.0291).

Conclusions: We found ambivalent results regarding the role of the markers as potential tumor suppressors, implying a context-dependent function of these molecules which might change in the course of time. DOK1 may play an inhibiting role in the serrated pathway. Remarkably, molecular markers have the potential to predict recurrence, since a combined expression analysis of high DOK1 and low MTMR7 correlated with the likelihood of segmental adenoma recurrence.

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Published

2021-12-21

How to Cite

1.
Gutting T, Merkel A, Fink DJ, Hetjens S, Weidner P, Yu Y, Kähler G, Ebert MP, Gaiser T, Burgermeister E, Belle S. Expression of the EGFR-RAS Inhibitory Proteins DOK1 and MTMR7 and its Significance in Colorectal Adenoma and Adenoma Recurrence. JGLD [Internet]. 2021 Dec. 21 [cited 2026 Jul. 18];30(4):446-55. Available from: https://www.jgld.ro/jgld/index.php/jgld/article/view/3681

Issue

Vol. 30 No. 4: December 2021

Section

Original Article