Study of the prediction system for clinical response to M-VAC neoadjuvant chemotherapy for bladder cancer.
Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of M-VAC, can manage micrometastasis and improve the prognosis. However, some patients suffer from severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting the response to the M-VAC therapy. We analyzed gene-expression profiles of biopsy materials from 40 invasive bladder cancers using a cDNA microarray consisting of 27 648 genes, after populations of cancer cells had been purified by laser-microbeam microdissection. We identified 14 predictive genes that were expressed differently between nine responder and nine non-responder tumors and devised a prediction-scoring system that clearly separated the responder group from the non-responder group. This system accurately predicted the clinical response for 19 of the 22 additional test cases. The group of patients with positive predictive scores had significantly longer survival times than that with negative scores. As real-time RT-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative RT-PCR-based prediction system that could be feasible for routine clinical use. Taken together, our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.
Takata
R
R
Department of Urology, Iwate Medical University, Iwate, Japan. rtakata@iwate-med.ac.jp
Obara
W
W
Fujioka
T
T
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D015653:Cystectomy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate