title: Prediction of the response to chemotherapy in advanced esophageal cancer by gene expression profiling of biopsy samples.
abstract: To improve the prognosis of advanced esophageal cancer, neoadjuvant chemotherapy (NACT) followed by surgery is a promising treatment strategy. NACT has been shown to improve the prognosis of responders. However, non-responders not only suffer from side-effects, but they also lose precious time to take advantage of other possible treatments. Therefore, it is crucial to establish a reliable method that allows prediction of response before chemotherapy. A biopsy sample can provide valuable information on the biological characteristics of an individual esophageal cancer, which can affect chemosensitivity. Comprehensive gene expression profiling (GEP) using oligonucleotide microarray covering 30,000 human probes was performed in 50 pretreatment endoscopic biopsy samples from 25 patients with esophageal squamous cell cancer (ESCC) who underwent cisplatin-based chemotherapy (two samples per patient). Chemotherapeutic responses were evaluated by the reduction rate of the tumor area on CT scans. Responders were defined as patients with reduction rates of ≥50% and non-responders were defined as patients with <50% decrease. The diagnostic system, that predicts responses to chemotherapy, was constructed with the 199 most informative genes, and showed 82% of accuracy. Furthermore, the predictive performance of this system was confirmed using an additional ten samples with an accuracy of 80%. This study shows that GEP of pretreatment ESCC biopsy samples has the potential to predict responses to chemotherapy.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Motoori
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Takamichi
authors.initials: T
authors.lastname: Komori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Takushi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D016000:Cluster Analysis; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil