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

Abstract

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.

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…Another study, based on NGS (Next Generation Sequencing) analysis, showed that KRAS mutation occurred in 63.6% of 22 Indonesian patients with mostly advanced CRC [42]. Distinct mutations located in codons 13, 14, 34, 58, 59, and 146 were found as opposed to more commonly reported mutations in codons 12, 13, 61, 146 [42][43][44]. A recent study in China has also reported that KRAS mutation was found in 69.4% of the early lesions [45,46].…”

Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer

“…Prior to our explorative study, we performed a systematic review to summarize the current knowledge on genetics and genomics in CRC-PM [ 19 ]. An NGS analysis with 409 cancer genes showed several additional genetic mutations, i.e., ARID1A , PKHD1 , UBR5 , PAX5 , TP53 , ASXL1 , and AR , presumably associated with PM [ 52 ].…”

“…The aim of this study was to identify genomic changes in primary CRC that are associated with development of PMs, which would allow early detection and personal and early patient treatment. Such a study has not been reported yet [ 17 , 19 ], despite the growing attention and possibilities for the genomic analysis of cancer using, for example, next-generation sequencing (NGS) techniques with broad gene panels investigating DNA and RNA alternations.…”

Prognostic Biomarkers of Cell Proliferation in Colorectal Cancer (CRC): From Immunohistochemistry to Molecular Biology Techniques

“…A recent review paper summarized the use of various molecular techniques (e.g., RT-PCR, PCR, and single nucleotide polymorphism (SNP) genotyping assay, NGS, NanoString analysis, Sanger sequencing, MassArray sequencing, quantitative MSP) to investigate changes at the DNA and RNA level that may predict CRC metastasis to the peritoneum. Only BRAF mutations were associated with peritoneal metastases in 10/17 studies [ 353 ].…”