Prognostic significance of MRE11 overexpression in colorectal cancer patients

Vincent Ho, Liping Chung, Kate Wilkinson, Vivienne Lea, Stephanie H. Lim, Askar Abubakar, Weng Ng, Mark Lee, Tara L. Roberts, Wei Chua, Cheok Soon Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Meiotic recombination 11 (MRE11) plays a critical role in the DNA damage response and maintenance of genome stability and is associated with the prognosis for numerous malignancies. Here, we explored the clinicopathological significance and prognostic value of MRE11 expression in colorectal cancer (CRC), a leading cause of cancer-related deaths worldwide. Samples from 408 patients who underwent surgery for colon and rectal cancer between 2006 and 2011, including a sub-cohort of 127 (31%) patients treated with adjuvant therapy, were analyzed. In Kaplan–Meier survival analyses, we found that high MRE11 expression in the tumor center (TC) was significantly associated with poor disease-free survival (DFS; p = 0.045) and overall survival (OS; p = 0.039). Intriguingly, high MRE11 expression in the TC was also significantly correlated with reduced DFS (p = 0.005) and OS (p = 0.010) in the subgroup with right-sided primary CRC. In multivariate analyses, high MRE11 expression (hazard ratio [HR] = 1.697, 95% confidence interval [CI]: 1.034–2.785; p = 0.036) and lymphovascular/perineural invasion (LVI/PNI; HR = 1.922, 95% CI 1.122–3.293; p = 0.017) showed significant association with worse OS in patients with right-sided tumors but not those with left-sided tumors. Moreover, in patients with right-sided tumors, high MRE11 was associated with worse OS for those with lymph node involvement (p = 0.006) and LVI/PNI (p = 0.049). Collectively, our results suggest that MRE11 may serve as an independent prognostic marker in those with right-sided severe CRC, with clinical value in the management of these patients.
Original languageEnglish
Article number2438
Number of pages17
JournalCancers
Volume15
Issue number9
Publication statusPublished - May 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Open Access - Access Right Statement

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Notes

WIP in RD

Keywords

  • MRE11
  • DNA damage response
  • biomarkers
  • colorectal cancer (CRC)
  • primary tumor site
  • prognosis
  • lymph node involvement

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