title: Copy number changes can be a predictor for hemoglobin reduction after S-1 monotherapy in gastric cancer.
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.
authors.affiliation: Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-Ku, Seoul 120-752, Korea.
authors.forename: Hei Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Chan Hee
authors.initials: CH
authors.lastname: Park
authors.forename: Chong-Kun
authors.initials: CK
authors.lastname: Im
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D018628:Gene Dosage; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D015996:Survival Rate; D005641:Tegafur / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D006454:Hemoglobins; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid