title: Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker genes and efficacy-prediction formulae using their expression data.
abstract: Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuvant chemotherapy gives a better chance of survival, we attempted to develop a chemosensitivity prediction model to improve individual responses to therapy. Comprehensive gene expression analyses (cDNA and oligonucleotide microarrays) and MTT assay of 8 drugs in 20 KYSE squamous cell carcinoma cell lines were performed to distinguish candidate marker genes whose expression levels reproducibly correlated with cellular drug sensitivities. After confirmation with real-time RT-PCR, we performed multiple regression analyses to develop drug-sensitivity prediction formulae using the quantified expression data of selected marker genes. Using the same sets of genes, we also constructed prediction models for individual clinical responses to 5-FU-based chemotherapy using 18 cases. We selected 5 better marker genes, known as drug sensitivity determinants, identified 9 novel predictive genes for 4 of 8 anticancer drugs [5-FU, CDDP, DOX, and CPT-11 (SN-38)], and developed highly predictive formulae of in vitro sensitivities to the 4 drugs and clinical responses to 5-FU-based adjuvant chemotherapies in terms of overall and disease-free survivals. Our selected genes are likely to be effective drug-sensitivity markers and formulae using the 9 novel genes would provide advantages in prediction.
authors.affiliation: Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shimokuni
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Hiyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Otani
authors.forename: Megu
authors.initials: M
authors.lastname: Ohtaki
authors.forename: Jun
authors.initials: J
authors.lastname: Hihara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Kawahara
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.forename: Takashi
authors.initials: T
authors.lastname: Aikou
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishiyama
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005819:Genetic Markers; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005819:Genetic Markers; D012334:RNA, Neoplasm