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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
MicroRNA Expression in KRAS- and BRAF-mutated Colorectal Cancers
Ida V Lundberg1, Maria L Wikberg2, Ingrid Ljuslinder3
1Department of Medical Biosciences, Pathology, Umeå University, Umea, Sweden ida.lundberg@umu.se.
Background/Aim:
KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS- and BRAF-mutated CRCs.
Materials And Methods:
Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.
Results:
Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.
Conclusion:
Our results suggest that KRAS- and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS- and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.
Insights
Colorectal cancer (CRC) with KRAS or BRAF mutations may have distinct microRNA (miRNA) profiles. While BRAF-mutated tumors showed altered miR-31 and miR-373 levels compared to wild-type, no differences were found between KRAS- and BRAF-mutated groups.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) frequently exhibits mutations in KRAS and BRAF genes.
- KRAS and BRAF mutations influence distinct clinical and histopathological features in CRC.
- Investigating microRNA (miRNA) expression may elucidate these clinicopathological differences.
Purpose of the Study:
- To determine if differential miRNA expression explains clinicopathological variations between KRAS- and BRAF-mutated CRCs.
- To identify specific miRNA signatures associated with KRAS and BRAF mutations in CRC.
Main Methods:
- Analyzed expression of 84 miRNAs in CRC cell lines using PCR array.
- Examined selected miRNAs (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, miR-373) in tumor tissues.
- Compared miRNA expression between wild-type, KRAS-mutated, and BRAF-mutated CRC samples.
Main Results:
- BRAF-mutated tumors showed significantly higher miR-31 and lower miR-373 expression compared to wild-type tumors.
- No significant differences in the analyzed miRNA expression levels were observed between KRAS-mutated and BRAF-mutated tumors.
Conclusions:
- KRAS- and BRAF-mutated CRCs might possess distinct miRNA signatures compared to wild-type CRC.
- The specific miRNAs analyzed in this study did not differentiate between KRAS- and BRAF-mutated tumors.
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