Association of miR-125b, miR-17 and let-7c Dysregulations With Response to Anti-epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With Metastatic Colorectal Cancer

被引:7
作者
Fiala, Ondrej [1 ,2 ,3 ]
Sorejs, Ondrej [1 ,2 ,3 ]
Hosek, Petr [3 ]
Liska, Vaclav [2 ,3 ,4 ]
Vycital, Ondrej [2 ,4 ]
Bruha, Jan [2 ,4 ]
Kucera, Radek [2 ,5 ]
Topolcan, Ondrej [2 ,5 ]
Finek, Jindrich [1 ,2 ]
Maceckova, Diana [3 ]
Pitule, Pavel [3 ]
机构
[1] Charles Univ Prague, Dept Oncol & Radiotherapeut, Fac Med, Alej Svobody 80, CZ-30460 Plzen, Czech Republic
[2] Charles Univ Prague, Univ Hosp Pilsen, Alej Svobody 80, CZ-30460 Plzen, Czech Republic
[3] Charles Univ Prague, Fac Med Pilsen, Biomed Ctr, Plzen, Czech Republic
[4] Charles Univ Prague, Dept Surg, Fac Med, Plzen, Czech Republic
[5] Charles Univ Prague, Dept Immunochem Diagnost, Fac Med, Plzen, Czech Republic
基金
欧盟地平线“2020”;
关键词
Colorectal cancer; cetuximab; panitumumab; chemotherapy; microRNA; miR-125b; miR-17; let-7c; RAS MUTATIONS; MICRORNAS; TUMOR; EXPRESSION; MECHANISM; KRAS; SUPPRESSOR; CETUXIMAB; EFFICACY; BENEFIT;
D O I
10.21873/cgp.20217
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: MicroRNAs (miRs) play an important role in the regulation of cancer-related processes and are promising candidates for cancer biomarkers. The aim of the study was to evaluate the association of response to anti-EGFR monoclonal antibodies (mAbs) with selected miR expression profiles, including miR-125b, let-7c, miR-99a, miR-17, miR-143 and miR-145 in metastatic colorectal cancer (mCRC) patients. Patients and Methods: This retrospective study included 46 patients with mCRC harbouring wild-type RAS gene treated with cetuximab or panitumumab combined with chemotherapy in first- or second-line therapy. The miR expression was assessed using qRT-PCR. Results: Down-regulation of miR-125b and let-7c and up-regulation of miR-17 were found in the tumour tissue (p=0.0226, p=0.0040, p<0.0001). Objective response rate (ORR) was associated with up-regulation of miR-125b (p=0.0005). Disease control rate (DCR) was associated with up-regulation of miR-125b and let-7c (p=0.0383 and p=0.0255) and down-regulation of miR-17 (p=0.0464). MiR-125b showed correlation with progression free and overall survival (p=0.055 and p=0.006). Conclusion: The results show that up-regulation of miR-125b is associated with higher ORR and DCR and longer survival; let-7c up-regulation and miR-17 downregulation are associated with higher DCR in mCRC patients treated with anti-EGFR mAbs.
引用
收藏
页码:605 / 613
页数:9
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