Copy number variation and clinical response to chemotherapy and bevacizumab in the Czech metastatic colorectal cancer patients
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články
PubMed
39174331
DOI
10.48095/ccko2024277
PII: 138288
Knihovny.cz E-zdroje
- Klíčová slova
- bevacizumab, colorectal cancer, colorectal carcinoma, structural genetic variation,
- MeSH
- bevacizumab * terapeutické užití MeSH
- kolorektální nádory * farmakoterapie genetika patologie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádorové biomarkery * genetika MeSH
- pilotní projekty MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- variabilita počtu kopií segmentů DNA * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- bevacizumab * MeSH
- nádorové biomarkery * MeSH
- protinádorové látky imunologicky aktivní MeSH
BACKGROUND: Despite bevacizumab being the first biological agent approved for the treatment of metastatic colorectal cancer (mCRC), there is not any established DNA biomarker to improve its efficacy and personalize the treatment. MATERIALS AND METHODS: Thirty patients with mCRC on bevacizumab therapy (15 with a good response and 15 with a poor response) from the University Hospital Olomouc were followed. Formalin-fixed paraffin-embedded (FFPE) samples were used for copy number variation (CNV) analysis using the OncoScan FFPE Assay Kit in order to capture approx. 900 tumor genes. RESULTS: In the group of good responding patients, 102 genes (classified as ATPases, type AAA, neuronal signal transmission, regulation of transcription, and superior domain PH type), potentially significant positive predictive tumor biomarkers of bevacizumab treatment, were found. In the poorly responding group, 74 potentially negative predictive genes (classified as galectines, Jak-STAT signalling pathway, MAPK cascade, differentiation, and F-box associated domain) were identified. CONCLUSION: In the pilot study, we found promising copy number variation biomarkers of bevacizumab response in FFPE samples of mCRC patients. The validation phase should be focused especially on the genes associated with angiogenesis (AGRN, MAPK8, ARHGAP22, LGALS13, LGALS4, ZFP36, and MYC), tumorigenesis (DVL1), and tumor proliferation (IFNL1, IFNL2, IFNL3, MAP3K10, and MAP4K1).
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