DNA and RNA Alterations Associated with Colorectal Peritoneal Metastases: A Systematic Review

D.J.I. Heuvelings*, A.G.W.E. Wintjens, J. Luyten, G.E.W.A. Wilmink, L. Moonen, E.J.M. Speel, I.H.J.T. de Hingh, N.D. Bouvy, A. Peeters

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review


Simple Summary Colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis. Currently, research has been ongoing to develop new treatment options for CRC patients with PM. DNA/RNA alterations identification in the primary tumor might help identify patients who are at high risk for developing PM postoperatively. These patients could benefit from preventive or early treatment. The aim of this systematic review is to create an overview of studies which analyzed genomic DNA and RNA expression alteration correlated to PM with the goal of identifying potentially predictive biomarkers. We included 32 studies investigating primary colorectal tumors of 18,906 patients. Only BRAF mutations were reported as significantly associated with PM in 10 of 17 studies. As no specific biomarkers in the primary tumors of CRC patients could have been identified, further research with comprehensive genomic profiling is still desirable. Background: As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment. Aim: To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied. Methods: A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines. Results: Overall, 32 studies with 18,906 patients were included. BRAF mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers. Conclusion: An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of BRAF mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required.
Original languageEnglish
Article number549
Number of pages31
Issue number2
Publication statusPublished - 1 Jan 2023


  • biomarkers
  • colorectal cancer
  • genetic mutations
  • peritoneal metastases
  • systematic review
  • RAS

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