title: Annexin A4 is a possible biomarker for cisplatin susceptibility of malignant mesothelioma cells.
abstract: Mesothelioma is a highly malignant tumor with a poor prognosis and limited treatment options. Although cisplatin (CDDP) is an effective anticancer drug, its response rate is only 20%. Therefore, discovery of biomarkers is desirable to distinguish the CDDP-susceptible versus resistant cases. To this end, differential proteome analysis was performed to distinguish between mesothelioma cells of different CDDP susceptibilities, and this revealed that expression of annexin A4 (ANXA4) protein was higher in CDDP-resistant cells than in CDDP-susceptible cells. Furthermore, ANXA4 expression levels were higher in human clinical malignant mesothelioma tissues than in benign mesothelioma and normal mesothelial tissues. Finally, increased susceptibility was observed following gene knockdown of ANXA4 in mesothelioma cells, whereas the opposite effect was observed following transfection of an ANXA4 plasmid. These results suggest that ANXA4 has a regulatory function related to the cisplatin susceptibility of mesothelioma cells and that it could be a biomarker for CDDP susceptibility in pathological diagnoses.
authors.affiliation: Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagano
authors.forename: So-ichiro
authors.initials: S
authors.lastname: Kanasaki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Maeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Furuya
authors.forename: Masaki
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nabeshi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Norio
authors.initials: N
authors.lastname: Itoh
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
mesh_terms: D017314:Annexin A4 / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D018301:Neoplasms, Mesothelial / Q000235:genetics / Q000378:metabolism*
chemical_list: D017314:Annexin A4; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D002945:Cisplatin