Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker genes and efficacy-prediction formulae using their expression data.
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.
Shimokuni
Tatsushi
T
Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
Tanimoto
Keiji
K
Hiyama
Keiko
K
Otani
Keiko
K
Ohtaki
Megu
M
Hihara
Jun
J
Yoshida
Kazuhiro
K
Noguchi
Tsuyoshi
T
Kawahara
Katsunobu
K
Natsugoe
Shoji
S
Aikou
Takashi
T
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Sato
Yuji
Y
Todo
Satoru
S
Hiyama
Eiso
E
Nishiyama
Masahiko
M
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
D000970:Antineoplastic Agents; D005819:Genetic Markers; D012334:RNA, Neoplasm