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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Amemia 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 ΔHb/cycle ≤1.0) or severe reduction group (SRG ΔHb/cycle >1.0). ΔHb/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 ≥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 × PTX1) + (0.211 × MYO5A) + (0.516 × 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.

Original languageEnglish
Pages (from-to)787-796
Number of pages10
JournalInternational journal of oncology
Volume34
Issue number3
DOIs
Publication statusPublished - 2009 Apr 20

Fingerprint

Stomach Neoplasms
Hemoglobins
Genes
Gene Dosage
Anemia
Appointments and Schedules
Logistic Models
Therapeutics
Oligonucleotide Array Sequence Analysis
Disease-Free Survival
Area Under Curve
Biomarkers
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jeung, Hei Cheul ; Rha, Sun Young ; Park, Chan Hee ; Im, Chong Kun ; Shin, Sang Joon ; Ahn, Joong Bae ; Noh, Sung Hoon ; Roh, Jae Kyung ; Chung, Hyun Cheol. / Copy number changes can be a predictor for hemoglobin reduction after S-1 monotherapy in gastric cancer. In: International journal of oncology. 2009 ; Vol. 34, No. 3. pp. 787-796.
@article{daff35185f39496ab328eebefd66095c,
title = "Copy number changes can be a predictor for hemoglobin reduction after S-1 monotherapy in gastric cancer",
abstract = "Amemia 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 ΔHb/cycle ≤1.0) or severe reduction group (SRG ΔHb/cycle >1.0). ΔHb/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 ≥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 × PTX1) + (0.211 × MYO5A) + (0.516 × 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.",
author = "Jeung, {Hei Cheul} and Rha, {Sun Young} and Park, {Chan Hee} and Im, {Chong Kun} and Shin, {Sang Joon} and Ahn, {Joong Bae} and Noh, {Sung Hoon} and Roh, {Jae Kyung} and Chung, {Hyun Cheol}",
year = "2009",
month = "4",
day = "20",
doi = "10.3892/ijo_00000204",
language = "English",
volume = "34",
pages = "787--796",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "3",

}

Copy number changes can be a predictor for hemoglobin reduction after S-1 monotherapy in gastric cancer. / Jeung, Hei Cheul; Rha, Sun Young; Park, Chan Hee; Im, Chong Kun; Shin, Sang Joon; Ahn, Joong Bae; Noh, Sung Hoon; Roh, Jae Kyung; Chung, Hyun Cheol.

In: International journal of oncology, Vol. 34, No. 3, 20.04.2009, p. 787-796.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Copy number changes can be a predictor for hemoglobin reduction after S-1 monotherapy in gastric cancer

AU - Jeung, Hei Cheul

AU - Rha, Sun Young

AU - Park, Chan Hee

AU - Im, Chong Kun

AU - Shin, Sang Joon

AU - Ahn, Joong Bae

AU - Noh, Sung Hoon

AU - Roh, Jae Kyung

AU - Chung, Hyun Cheol

PY - 2009/4/20

Y1 - 2009/4/20

N2 - Amemia 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 ΔHb/cycle ≤1.0) or severe reduction group (SRG ΔHb/cycle >1.0). ΔHb/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 ≥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 × PTX1) + (0.211 × MYO5A) + (0.516 × 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.

AB - Amemia 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 ΔHb/cycle ≤1.0) or severe reduction group (SRG ΔHb/cycle >1.0). ΔHb/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 ≥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 × PTX1) + (0.211 × MYO5A) + (0.516 × 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.

UR - http://www.scopus.com/inward/record.url?scp=64549085019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64549085019&partnerID=8YFLogxK

U2 - 10.3892/ijo_00000204

DO - 10.3892/ijo_00000204

M3 - Article

C2 - 19212683

AN - SCOPUS:64549085019

VL - 34

SP - 787

EP - 796

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 3

ER -