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Comprehensive molecular analysis to predict the efficacy ofchemotherapy containing bevacizumab in patients with metastaticcolorectal cancer

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肿瘤学研究(英文) 2023年第6期31卷 855-866页

作者： SUNG HEE LIM HEE JIN CHO KYOUNG-MEE KIM HO YEONG LIM WON KI KANG JEEYUN LEE YOUNG SUK PARK HEE CHEOL KIM SEUNG TAE KIM Division of Hematology/Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea Precision Medicine Research Institute Samsung Medical CenterGangnam-guSeoul06351Korea Department of Biomedical Convergence Science and Technology Kyungpook National UniversityDaegu41566Korea Department of Pathology and Translational Genomics Samsung Medical CenterSungkyunkwan University School of MedicineSeoul06351Korea Department of Surgery Samsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea

Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been ***:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing *** molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient ***:Genomic and molecularcharacterization was successfully conducted in 103 *** of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite *** those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to *** the four SRCCs,two were CMS1,one was CMS4,and the other was *** status was a significantly enriched factor in responders to bevacizumab *** growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in ***,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX ***),thesignificance of the molecular pathways varied according to the backbone ***:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing *** need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic oppor

关键词： Bevacizumab Whole-exome sequencing Ribonucleic acid sequencing methylation array Colorectal cancer

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