Proteome-based identification of molecular markers predicting chemosensitivity to each category of anticancer agents in human gliomas.
To identify the protein markers that are clinically useful for predicting efficacy of anticancer agents, we investigated the correlation between the proteome profiling patterns and the in vitro chemosensitivity in human gliomas. The proteome of 93 surgical samples were analyzed with two-dimensional gel electrophoresis (2DE) and mass spectrometry. The in vitro chemosensitivities to 10 different kinds of anticancer agents (cyclophosphamide, nimustine, cisplatin, cytosine arabinoside, mitomycin C, peplomycin, adriamycin, etoposide, vincristine, paclitaxel) were measured by flow cytometric detection of apoptosis. We identified a set of 41 proteins that significantly affected the in vitro chemosensitivity to each category of anticancer agents. Many of the proteins that correlated with chemoresistance were categorized into the signal transduction proteins including the G-proteins. The present study showed that the proteome analysis using 2DE could provide a list of proteins that may be the potential predictive markers for chemosensitivity in human gliomas. They can also be direct and rational targets for anti-glioma therapy and be used for sensitization to the conventional chemotherapeutic regimens.
Iwadate
Yasuo
Y
Department of Neurological Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. iwadatey@faculty.chiba-u.jp
Sakaida
Tsukasa
T
Saegusa
Takashi
T
Hiwasa
Takaki
T
Takiguchi
Masaki
M
Fujimoto
Shuichi
S
Yamaura
Akira
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D011237:Predictive Value of Tests; D011379:Prognosis; D020543:Proteome; D015398:Signal Transduction
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D020543:Proteome