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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
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Germline variation in RASAL2 may predict survival in patients with RAS-activated colorectal cancer
Christopher Wills1, Katie Watts1, Timothy S Maughan2
1Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
Genes, Chromosomes & Cancer
|February 15, 2023
Summary
RASAL2 is a significant gene associated with survival in patients with RAS mutant colorectal cancer (CRC). The rs12028023 SNP in RASAL2 may serve as a therapeutic target for CRC patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Colorectal cancer (CRC) with RAS mutations requires targeted therapies.
- Mitogen-activated protein kinase (MAPK) pathway mutations are common in advanced CRC.
Purpose of the Study:
- Identify potential drug targets for RAS mutant CRC.
- Investigate the prognostic role of the RASAL2 gene in CRC survival.
Main Methods:
- Genome-wide association study (GWAS) and survival data analysis in 694 patients with MAPK-activated CRC.
- Analysis of single nucleotide polymorphism (SNP) rs12028023 in RASAL2 for its association with survival and tumor characteristics.
Main Results:
- RASAL2 was the most significant gene associated with survival in MAPK-activated CRC (p = 2.0 × 10⁻⁵).
- The minor allele (A) of rs12028023 in RASAL2 was linked to a 167-day increase in median survival.
- rs12028023 improved survival in RAS mutant CRC but not BRAF mutant CRC, and was associated with reduced tumor size and RASAL2 expression.
Conclusions:
- RASAL2 plays a prognostic role in MAPK-activated CRC.
- The rs12028023 SNP in RASAL2 shows potential as a therapeutic target for CRC.
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