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Copy number changes can be a predictor for hemoglobin reduction after S-1 monotherapy in gastric cancer

Authors
 HEI CHEUL JEUNG  ;  SUN YOUNG RHA  ;  CHAN HEE PARK  ;  CHONG-KUN IM  ;  SANG JOON SHIN  ;  JOONG BAE AHN  ;  SUNG HOON NOH  ;  JAE KYUNG ROH  ;  HYUN CHEOL CHUNG 
Citation
 INTERNATIONAL JOURNAL OF ONCOLOGY, Vol.34(3) : 787-796, 2009 
Journal Title
INTERNATIONAL JOURNAL OF ONCOLOGY
ISSN
 1019-6439 
Issue Date
2009
MeSH
Adult ; Aged ; Anemia/blood ; Anemia/chemically induced* ; Anemia/genetics ; Antimetabolites, Antineoplastic/adverse effects* ; Antimetabolites, Antineoplastic/therapeutic use ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Combinations ; Female ; Gene Dosage* ; Hemoglobins/metabolism* ; Humans ; Male ; Middle Aged ; Oxonic Acid/adverse effects* ; Oxonic Acid/therapeutic use ; Stomach Neoplasms/blood* ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/genetics ; Survival Rate ; Tegafur/adverse effects* ; Tegafur/therapeutic use ; Treatment Outcome
Abstract
Anemia is a unique side effect in Korean gastric cancer patients after S-1 monotherapy. We studied gastric cancer patients from a phase II trial of S-1 monotherapy with a 2-week treatment and 1-week rest schedule. Patients from a phase II trial of S-1 monotherapy with a 4-week treatment and 2-week rest were used as a reference group. The patients were categorized into two groups based on the degree of hemoglobin reduction per cycle of S-1: the mild reduction group (MRG DeltaHb/cycle < or =1.0) or severe reduction group (SRG DeltaHb/cycle >1.0). DeltaHb/cycle was calculated from maximum reduction of hemoglobin per one cycle of the treatment. Microarray-CGH was performed using a 17K cDNA microarray containing 15,723 unique genes. We selected genes with copy number variation defined as amplification (log2R/G >0.68) or deletion (log2R/G <-0.68), and a genetic aberration frequency difference of > or =30% between the MRG and the SRG. There were no differences in clinical factors, S-1 treatment-related factors (dose, dose intensity), toxicity, S-1 metabolism-related gene copy numbers (CYP2A6, DPD), or progression-free survival between the MRG and the SRG. Three genes were selected from microarray-CGH and logistic regression model: logit LN(Z) = (1.321) + (1.038 x PTX1) + (0.211 x MYO5A) + (0.516 x ZNF664). In the SRG, all 3 genes showed a trend of higher copy numbers than the MRG. There were no common anemia-related genes identified from different chemotherapy schedule of S-1 monotherapy. The logistics obtained from 3 genes predicted the hemoglobin reduction with an accuracy of 78%. The AUC was 0.744 for the final regression model. The combined copy number changes of the 3 genes can be developed into a biomarker in predicting S-1 treatment-related anemia.
Full Text
http://www.spandidos-publications.com/ijo/34/3/787?text=abstract
DOI
10.3892/ijo_00000204
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Roh, Jae Kyung(노재경)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Im, Chong Kun(임종근)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103784
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