期刊
VIRCHOWS ARCHIV
卷 478, 期 4, 页码 695-705出版社
SPRINGER
DOI: 10.1007/s00428-020-02983-6
关键词
Lung metastasis; Metastatic colorectal cancer; Biomarker; CD133; β -catenin; MAPK pathway mutations
类别
资金
- Projekt DEAL
- Scholarship for excellent young scientists as part of the Bavarian Equal Opportunities Fund
- Association for the Promotion of Science and Research at the Medical Faculty of the Ludwig-Maximilians-University Munich
This study found that different patterns of distant spread in colorectal cancer are associated with specific biomarker alterations, indicating potential different molecular subtypes of the disease.
Metastatic spread is the most important life-threatening feature of colorectal cancer and is supposed to be mainly driven by alterations in different carcinogenic pathways. The present study compared mutation and expression profiles of distinctive biomarkers in colorectal cancer patients with different clinical metastatic patterns. As for a case-control study, patients were matched according to T category, grading and primary tumour site. Overall, 246 patients with either exclusive lung metastasis (N = 82), exclusive liver metastasis (N = 82) or non-metastatic colorectal cancer (N = 82) were identified. Paraffin-embedded specimens were examined for mutations in the RAS and RAF genes and for the expression of beta-catenin and CD133. Clinical endpoints were presence or absence of distant metastasis, formation of metastasis in lungs versus the liver and survival. MAPK pathway mutations in either the KRAS, NRAS or BRAF gene were associated with the development of lung metastasis (63.4%) compared to the control group (47.6%; p = 0.04). MAPK pathway alterations plus high beta-catenin expression were associated with metastasis to the lungs but not to the liver (28.0% vs. 13.4%; p = 0.02). High CD133 expression correlated with the development of liver metastasis compared to the control group (30.5% vs. 14.6%; p = 0.02). This data indicates that different patterns of distant spread are associated with specific biomarker alterations and may represent different molecular subtypes of colorectal cancer. However, underlying mechanisms of metastasis formation in different anatomic sites remains unclear. Since knowledge of the anticipated site of distant spread would substantially impact clinical management, further research is needed to identify solid biomarkers for different metastatic patterns.
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