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.
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.
Authors: Kayla L Conner; Asra N Shaik; Elmira Ekinci; Seongho Kim; Julie J Ruterbusch; Michele L Cote; Steve M Patrick Journal: DNA Repair (Amst) Date: 2020-01-16
Authors: Malcolm H Lawson; Natalie M Cummings; Doris M Rassl; Roslin Russell; James D Brenton; Robert C Rintoul; Gillian Murphy Journal: Cancer Res Date: 2011-06-03 Impact factor: 12.701