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Review
. 2021 Apr;12(Suppl 1):S191-S203.
doi: 10.21037/jgo-20-136.

Omics analyses in peritoneal metastasis-utility in the management of peritoneal metastases from colorectal cancer and pseudomyxoma peritonei: a narrative review

Affiliations
Review

Omics analyses in peritoneal metastasis-utility in the management of peritoneal metastases from colorectal cancer and pseudomyxoma peritonei: a narrative review

Christin Lund-Andersen et al. J Gastrointest Oncol. 2021 Apr.

Abstract

High-throughput "-omics" analysis may provide a broader and deeper understanding of cancer biology to define prognostic and predictive biomarkers and identify novel therapy targets. In this review we provide an overview of studies where the peritoneal tumor component of peritoneal metastases from colorectal cancer (PM-CRC) and pseudomyxoma peritonei (PMP) were analyzed. Most of the available data was derived from DNA mutation analysis, but a brief review of findings from transcriptomic and protein expression analysis was also performed. Studies reporting genomic analysis of peritoneal tumor samples from 1,779 PM-CRC and 623 PMP cases were identified. The most frequently mutated genes in PM-CRC were KRAS, APC, SMAD4, BRAF, and PIK3CA, while in PMP KRAS, GNAS, FAT4, TGFBR1, TP53 and SMAD3/4 mutations were most commonly identified. Analyses were performed by single-gene analyses and to some extent targeted next-generation sequencing, and a very limited amount of broad explorative data exists. The investigated cohorts were typically small and heterogeneous with respect to the methods used and to the reporting of clinical data. This was even more apparent regarding transcriptomic and protein data, as the low number of cases examined and quality of clinical data would not support firm conclusions. Even for the most frequently mutated genes, the results varied greatly; for instance, KRAS mutations were reported at frequencies between 20-57% in PM-CRC and 38-100% in PMP. Such variation could be caused by random effects in small cohorts, heterogeneity in patient selection, or sensitivity of applied technology. Although a large number of samples have been subjected to analysis, cross-study comparisons are difficult to perform, and combined with small cohorts and varying quality and detail of clinical information, the observed variation precludes useful interpretation in a clinical context. Although omics data in theory could answer questions to aid management decisions in PM-CRC and PMP, the existing data does not presently support clinical implementation. With the necessary technologies being generally available, the main challenge will be to obtain sufficiently large, representative cohorts with adequate clinical data and standardized reporting of results. Importantly, studies where the focus is specifically on peritoneal disease are needed, where the study designs are aligned with clearly defined research questions to allow robust conclusions. Such studies are highly warranted if patients with PM-CRC and PMP are to derive benefit from recent advances in precision cancer medicine.

Keywords: Peritoneal metastasis (PM); colorectal cancer (CRC); genomics; pseudomyxoma peritonei (PMP); transcriptomics.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-136). The focused issue was sponsored by the Peritoneal Surface Oncology Group International (PSOGI). The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
Overview of the number of samples (N) subjected to omics analysis in PM-CRC (upper panel, 22 studies included) and PMP (lower panel, 21 studies included), also showing the distribution between methods used within the field of genomics. PCR, polymerase chain reaction (including Luminex technology and High-Resolution Melting); Sanger, Sanger sequencing, NGS, next generation sequencing, CNV, copy number variation; PM-CRC, peritoneal metastases from colorectal cancer; PMP, pseudomyxoma peritonei.

Comment in

  • Genetic targets for cancer control are a reality.
    Sugarbaker PH, Van der Speeten K. Sugarbaker PH, et al. J Gastrointest Oncol. 2021 Apr;12(Suppl 1):S204-S205. doi: 10.21037/jgo-2020-18. J Gastrointest Oncol. 2021. PMID: 33970166 Free PMC article. No abstract available.

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