Danique Heuvelings

263 DNA and RNA alterations associated with colorectal peritoneal metastases: A systematic review profiles and concluded that hsa-mri-31-5p seems to be overexpressed in patients with PM 24. The authors reported a set of 31 miRNAs which were significantly upregulated in the PM group, while ten miRNAs were found to be repressed as compared to LM. Another set of two miRNAs was significantly upregulated in the PM group, while 25 were found to be repressed as compared to no metastases. Shirahata et al. discovered a trend toward preferentially developing PM in tumors with Vimentin methylation, although this was not significant 41. Results of Broader Panel Analyses Lee et al. performed a broader panel analysis of which the results (ARID1A, PKHD1, UBR5, PAX5, TP53, ASXL1 and AR) are already described in Section 3.6.4 30. Jacob et al. explored gene expression profiles with a broad cancer “panel” comparing four groups (without metastases, with LM, with PM, and with both LM and PM) 25. They report that “18 genes had significantly different expression rates”, but they did not describe which genes. In another study, in which three groups were compared (without metastases, with LM, and with PM), the authors reported no significant down- or upregulation of distinct gene sets 26. All details about the reported genes and corresponding conclusions are described in The Supplementary. A conclusive summary for all genes is displayed in Figure 6. Figure 6. Overview of genes investigated with conclusions formulated by the authors of included studies. MSI Status In addition to DNA and RNA alterations, microsatellite instability (MSI) status was reported in ten articles 21, 28, 34, 35, 37, 43, 45, 46, 48, 50. Tran et al. describe the impact of BRAF mutations in combination with MSI status on the pattern of metastatic spread and its prognosis 48. The authors report that patients with MSI tumors show poorer survival in mCRC, and this is due to the association with BRAF mutations. Yang et al. state that MSI is associated with RET mutations 50. 11

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