Variabilita počtu kopií genů a léčebná odpověď na chemoterapii a bevacizumab u českých pacientů s metastatickým karcinomem kolorekta

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Autoři: 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
Působiště autorů: 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
Vyšlo v časopise: Klin Onkol 2024; 37(4): 277-285
Kategorie: Původní práce
doi: https://doi.org/10.48095/ccko2024277

Souhrn

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

Zdroje

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