Variabilita počtu kopií genů a léčebná odpověď na chemoterapii a bevacizumab u českých pacientů s metastatickým karcinomem kolorekta
Authors:
J. Stránská 1,2; K. Bartáková 1; Z. Rožánková 1; L. Kotková 1; J. Vrbková 1; R. Trojanec 1; P. Flodr 3; H. Jurtíková 1,2; B. Líznerová 1,2; J. Drábek 1,2
Authors‘ workplace:
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
1; University Hospital Olomouc, Czech Republic
2; Institute of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
3
Published in:
Klin Onkol 2024; 38(4): 277-285
Category:
Original Articles
doi:
https://doi.org/10.48095/ccko2024277
Overview
Východiska: Přestože je bevacizumab prvním biologickým léčivem schváleným pro léčbu metastatického kolorektálního karcinomu (mCRC), neexistuje žádný zavedený DNA biomarker, který by zlepšil jeho účinnost a personalizoval léčbu. Materiál a metody: Sledováno bylo 30 pacientů s mCRC na terapii bevacizumabem (15 s dobrou odpovědí a 15 se špatnou odpovědí) z Fakultní nemocnice Olomouc. Pro analýzu variací v počtu kopií genů (copy number variation – CNV) byly použity vzorky FFPE a OncoScan FFPE Assay Kit, který zachycuje přibližně 900 nádorových genů. Výsledky: Ve skupině dobře reagujících pacientů bylo jako potenciálně významné pozitivní prediktivní nádorové biomarkery léčby bevacizumabem identifikováno 102 genů (klasifikovaných jako ATPázy, typ AAA, neuronální přenos signálu, regulace transkripce a domény typu PH superior). Ve špatně reagující skupině bylo identifikováno 74 potenciálně negativních prediktivních genů (klasifikovaných jako galektiny, signální dráha Jak-STAT, kaskáda MAPK, diferenciace a doména asociovaná s F-boxem). Závěr: V pilotní studii jsme našli slibné biomarkery variace počtu kopií odpovědi na bevacizumab v FFPE vzorcích nádorů pacientů s mCRC. Validační fáze by měla být zaměřena zejména na geny spojené s angiogenezí (AGRN, MAPK8, ARHGAP22, LGALS13, LGALS4, ZFP36 a MYC), tumorigenezí (DVL1) a proliferací tumoru (IFNL1, IFNL2, IFNL3, MAP3K10 a MAP4K1).
Klíčová slova:
bevacizumab – kolorektální karcinom – variabilita počtu kopií segmentů DNA
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