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:8
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
相关论文
共 47 条
[1]   Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer [J].
Amado, Rafael G. ;
Wolf, Michael ;
Peeters, Marc ;
Van Cutsem, Eric ;
Siena, Salvatore ;
Freeman, Daniel J. ;
Juan, Todd ;
Sikorski, Robert ;
Suggs, Sid ;
Radinsky, Robert ;
Patterson, Scott D. ;
Chang, David D. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (10) :1626-1634
[2]   Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer [J].
Arndt, Greg M. ;
Dossey, Lesley ;
Cullen, Lara M. ;
Lai, Angela ;
Druker, Riki ;
Eisbacher, Michael ;
Zhang, Chunyan ;
Tran, Nham ;
Fan, Hongtao ;
Retzlaff, Kathy ;
Bittner, Anton ;
Raponi, Mitch .
BMC CANCER, 2009, 9 :374
[3]   Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues [J].
Bandres, E. ;
Cubedo, E. ;
Agirre, X. ;
Malumbres, R. ;
Zarate, R. ;
Ramirez, N. ;
Abajo, A. ;
Navarro, A. ;
Moreno, I. ;
Monzo, M. ;
Garcia-Foncillas, J. .
MOLECULAR CANCER, 2006, 5 (1)
[4]   Good guy or bad guy: the opposing roles of microRNA 125b in cancer [J].
Banzhaf-Strathmann, Julia ;
Edbauer, Dieter .
CELL COMMUNICATION AND SIGNALING, 2014, 12
[5]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[6]   The role of let-7 in cell differentiation and cancer [J].
Boyerinas, Benjamin ;
Park, Sun-Mi ;
Hau, Annika ;
Murmann, Andrea E. ;
Peter, Marcus E. .
ENDOCRINE-RELATED CANCER, 2010, 17 (01) :F19-F36
[7]   MicroRNA Signature in Metastatic Colorectal Cancer Patients Treated With Anti-EGFR Monoclonal Antibodies [J].
Cappuzzo, Federico ;
Sacconi, Andrea ;
Landi, Lorenza ;
Ludovini, Vienna ;
Biagioni, Francesca ;
D'Incecco, Armida ;
Capodanno, Alessandra ;
Salvini, Jessica ;
Corgna, Enrichetta ;
Cupini, Samanta ;
Barbara, Cecilia ;
Fontanini, Gabriella ;
Crino, Lucio ;
Blandino, Giovanni .
CLINICAL COLORECTAL CANCER, 2014, 13 (01) :37-U62
[8]   Hypermethylation-Associated Silencing of miR-125a and miR-125b: A Potential Marker in Colorectal Cancer [J].
Chen, Hui ;
Xu, Zhiying .
DISEASE MARKERS, 2015, 2015
[9]   MicroRNA-145: a potent tumour suppressor that regulates multiple cellular pathways [J].
Cui, Shi-Yun ;
Wang, Rui ;
Chen, Long-Bang .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2014, 18 (10) :1913-1926
[10]   The colorectal microRNAome [J].
Cummins, JM ;
He, YP ;
Leary, RJ ;
Pagliarini, R ;
Diaz, LA ;
Sjoblom, T ;
Barad, O ;
Bentwich, Z ;
Szafranska, AE ;
Labourier, E ;
Raymond, CK ;
Roberts, BS ;
Juhl, H ;
Kinzler, KW ;
Vogelstein, B ;
Velculescu, VE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (10) :3687-3692