@Article{or.2023.030374,
AUTHOR = {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},
TITLE = {Comprehensive molecular analysis to predict the efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer},
JOURNAL = {Oncology Research},
VOLUME = {31},
YEAR = {2023},
NUMBER = {6},
PAGES = {855--866},
URL = {http://www.techscience.com/or/v31n6/54217},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Although bevacizumab is an important treatment for metastatic colorectal cancer (CRC), not all patients with CRC benefit from it; in unselected patient populations, only modest survival benefits have been reported. <b>Methods:</b> We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identify biomarkers for a response to bevacizumab-containing treatment. The molecular analysis comprised whole-exome sequencing, ribonucleic acid sequencing, and a methylation array on patient tissues. <b>Results:</b> Genomic and molecular characterization was successfully conducted in 103 patients. Six of 103 CRC samples were hypermutated, and none of the non-hypermutant tumors were microsatellite unstable. Among 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 ADC. Of the four SRCCs, two were CMS1, one was CMS4, and the other was CMS3. <i>APC</i> mutation status was a significantly enriched factor in responders to bevacizumab treatment. Fibroblast growth factor receptor (FGFR) 1/2 signaling was upregulated in non-responders, whereas cell cycle, transfer ribonucleic acid processing, nucleotide excision repair, and oxidative phosphorylation pathways were enriched in responders. In addition, <i>IGF1</i> was differentially expressed in non-responders (log2 fold change = −1.43, <i>p</i> = 4.11 × 10<sup>−5</sup>, false discovery rate = 0.098), and <i>FLT1</i> was highly methylated in non-responders (<i>p</i> = 7.55 × 10<sup>−3</sup>). When the molecular pathways were reanalyzed separately according to the backbone chemotherapy (FOLFOX <i>vs</i>. FOLFIRI), the significance of the molecular pathways varied according to the backbone chemotherapy. <b>Conclusions:</b> This study sought a subset of CRC patients with a distinct clinical response to chemotherapy containing bevacizumab. Our results need to be validated in a large group of homogenous patient cohort and examined according to the different chemotherapy backbones to create personalized therapeutic opportunities in CRC.},
DOI = {10.32604/or.2023.030374}
}