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A platinum agent resistance gene, POLB , is a prognostic indicator in colorectal cancer
Author(s) -
Iwatsuki Masaaki,
Mimori Koshi,
Yokobori Takehiko,
Tanaka Fumiaki,
Tahara Koichiro,
Inoue Hiroshi,
Baba Hideo,
Mori Masaki
Publication year - 2009
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21275
Subject(s) - oxaliplatin , colorectal cancer , cisplatin , medicine , chemotherapy , metastasis , cancer research , oncology , cancer
Background Recent progress in chemotherapy with platinum agents has improved clinical outcome in colorectal cancer (CRC), but there are no useful markers to predict the efficacy of such agents. DNA polymerase beta ( POLB ) mediates the efficacy of chemotherapy through DNA repair machinery. We analyzed the significance of POLB expression in CRC chemotherapy and its potential as a prognostic indicator. Methods Using microarray, POLB was found to be overexpressed in CRC cells compared with corresponding normal colon epithelial cells. We determined the susceptibility of POLB ‐suppressed cells to cisplatin and oxaliplatin. We evaluated POLB mRNA expression in 97 CRC cases to determine the clinicopathologic significance of POLB expression. Results We found the suppression of POLB altered the in vitro susceptibility to cisplatin but not to oxaliplatin. In 97 CRC cases, lymph node metastasis, distant metastasis and TNM classification were significantly greater in the high POLB group than in the low group ( P < 0.05). Patients with high POLB expression had significantly poorer prognosis than those with low expression ( P < 0.05). Conclusions The data indicate POLB is overexpressed in CRC cases with high malignant potential. We suggest POLB could be useful as a predictive marker for selection of patients responsive to cisplatin. J. Surg. Oncol. 2009;100:261–266. © 2009 Wiley‐Liss, Inc.