Prediction of high-risk patients by genome-wide copy number alterations from remaining cancer after neoadjuvant chemotherapy and surgery.
In breast cancer, changes of gene copy number were analyzed by cDNA microarray-based comparative genome hybridization using post-treatment archived tissues. Genomic DNA was extracted from 45 surgical specimens after chemotherapy. Informative genes were selected by t-test and were statistically validated by prediction analysis using support vector machine in R package. Fluorescence in situ hybridization and quantitative PCR were performed for validation. We developed three clinical models: comparing good vs. poor prognosis (I), comparing good vs. poor prognosis among poor responders (II) and among good responders (III). 158 gene set (I) differentiated high and low risk of relapse group with 92% accuracy. 51 gene set (II) differentiated good and poor prognosis subgroups among poor responders with 99.9% accuracy. 32 gene set (III) differentiated good and poor prognosis subgroups among good responders with 96% accuracy. This approach has potential applications in the identification of high risk of recurrence after neoadjuvant chemotherapy and surgery.
Rha
Sun Young
SY
Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul 120-752, Korea.
Jeung
Hei Cheul
HC
Seo
Min Young
MY
Kim
Sang Cheol
SC
Yang
Woo Ick
WI
Moon
Yong Wha
YW
Chung
Hyun Cheol
HC
D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012307:Risk Factors