Genome-wide identification of possible methylation markers chemosensitive to targeted regimens in colorectal cancers

作者: Jin C. Kim , Han C. Lee , Dong H. Cho , Eun Y. Choi , Yoon K. Cho

DOI: 10.1007/S00432-011-1036-7

关键词: Internal medicineCetuximabFOLFIRITargeted therapyChemosensitivity assayMedicineBevacizumabMethylationColorectal cancerOncologyFOLFOX

摘要: Few efficient methylation markers of chemosensitivity have been discovered. The genome-wide analysis is needed to identify chemosensitive candidates targeted therapy. This study describes a two-step process select genes. A screening genes was performed using Beadarray and an in vitro assay 119 colorectal cancers (CRCs). Ten candidate identified during the initial were verified by biological utility assessment cell viability assays transfected CRC cells. Five related sensitivity bevacizumab regimens (RASSF1, MMP25, KCNQ1, ESR1, GALR2) or cetuximab (SCL18A2, GPX7, NID2, IGFBP3, ALX4) chosen first step. revealed that GALR2-overexpressing HCT116 cells significantly more than control (P = 0.022 0.019 for with FOLFIRI FOLFOX, respectively), concurrently on caspase-3 activity assay. GPX7- ALX4-overexpressed RKO less viable compared (GPX7: P = 0.027 each FOLFOX; ALX4: P = 0.049 0.003 but not prominent GPX7-overexpressed Two novel genes, GALR2 ALX4, as regimens, respectively. As our did include clinical association study, two should be validated large cohorts, hopefully predicting responsive patients regimens.

参考文章(31)
Jean M. Sargent, The Use of the MTT Assay to Study Drug Resistance in Fresh Tumour Samples Recent results in cancer research. ,vol. 161, pp. 13- 25 ,(2003) , 10.1007/978-3-642-19022-3_2
Richard Fox, Martine Aubert, Flow cytometric detection of activated caspase-3. Methods of Molecular Biology. ,vol. 414, pp. 47- 56 ,(2008) , 10.1007/978-1-59745-339-4_5
Jin C. Kim, Seon Y. Kim, Dong H. Cho, Ye J. Ha, Eun Y. Choi, Chan W. Kim, Seon A. Roh, Tae W. Kim, Hyoungseok Ju, Yong S. Kim, Novel Chemosensitive Single-Nucleotide Polymorphism Markers to Targeted Regimens in Metastatic Colorectal Cancer Clinical Cancer Research. ,vol. 17, pp. 1200- 1209 ,(2011) , 10.1158/1078-0432.CCR-10-1907
R. Stephanie Huang, Shiwei Duan, Sunita J. Shukla, Emily O. Kistner, Tyson A. Clark, Tina X. Chen, Anthony C. Schweitzer, John E. Blume, M. Eileen Dolan, Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach. American Journal of Human Genetics. ,vol. 81, pp. 427- 437 ,(2007) , 10.1086/519850
Hu Zhao, Kyoko Oka, Pablo Bringas, Vesa Kaartinen, Yang Chai, TGF-β type I receptor Alk5 regulates tooth initiation and mandible patterning in a type II receptor-independent manner Developmental Biology. ,vol. 320, pp. 19- 29 ,(2008) , 10.1016/J.YDBIO.2008.03.045
Katsuhiko Nosho, Natsumi Irahara, Kaori Shima, Shoko Kure, Gregory J. Kirkner, Eva S. Schernhammer, Aditi Hazra, David J. Hunter, John Quackenbush, Donna Spiegelman, Edward L. Giovannucci, Charles S. Fuchs, Shuji Ogino, Comprehensive Biostatistical Analysis of CpG Island Methylator Phenotype in Colorectal Cancer Using a Large Population-Based Sample PLoS ONE. ,vol. 3, pp. e3698- ,(2008) , 10.1371/JOURNAL.PONE.0003698
Sabine Maier, Christina Dahlstroem, Carolina Haefliger, Achim Plum, Christian Piepenbrock, Identifying DNA Methylation Biomarkers of Cancer Drug Response American Journal of Pharmacogenomics. ,vol. 5, pp. 223- 232 ,(2005) , 10.2165/00129785-200505040-00003
Matthias P.A. Ebert, Fabian Model, Suzanne Mooney, Kari Hale, Joe Lograsso, Lori Tonnes–Priddy, Juliane Hoffmann, Antal Csepregi, Christoph Röcken, Bela Molnar, Hans–Ulrich Schulz, Peter Malfertheiner, Catherine Lofton–Day, Aristaless-like Homeobox-4 Gene Methylation Is a Potential Marker for Colorectal Adenocarcinomas Gastroenterology. ,vol. 131, pp. 1418- 1430 ,(2006) , 10.1053/J.GASTRO.2006.08.034
Wade D Van Horn, Carlos G Vanoye, Charles R Sanders, Working model for the structural basis for KCNE1 modulation of the KCNQ1 potassium channel Current Opinion in Structural Biology. ,vol. 21, pp. 283- 291 ,(2011) , 10.1016/J.SBI.2011.01.001
Hyun Chang, Sun Young Rha, Hei-Cheul Jeung, Jae-Jun Jung, Tae Soo Kim, Ho Jeong Kwon, Byung Soo Kim, Hyun Cheol Chung, Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells Journal of Cancer Research and Clinical Oncology. ,vol. 136, pp. 1901- 1913 ,(2010) , 10.1007/S00432-010-0849-0