Elevated p53 and p21waf1 mRNA expression in blood lymphocytes from lung cancer patients with chemoresistance.
BACKGROUND
Clinical and experimental studies suggest that alteration of the expression level of the p53 gene and other damage responsive genes may be associated with chemoresistance in cancer patients.


METHODS
The present study evaluated the differences of the basal levels of lymphocytic p53 and p21waf1 mRNA expression collected before receiving cisplatin-based chemotherapy between 48 chemo-ineffective lung cancer patients and 39 chemo-effective lung cancer patients using an optimized semi-quantitative multiplex reverse transcriptase-polymerase chain reaction (RT-PCR).


RESULTS
The data indicated that the mean mRNA level of p53 gene in chemo-ineffective patients (0.66) was 26.9% higher than that of the chemo-effective patients (0.52) with statistical significance (P=0.03), and a significantly higher level of p21waf1 mRNA expression in the chemo-ineffective patients (P=0.03) was also observed. In addition, by the multiplex long quantitative PCR analysis, we demonstrated that chemo-ineffective and chemo-effective patients have similar amounts of UV damage on their p53 gene of lymphocyte DNA through equal UV treatment.


CONCLUSIONS
Our results suggest that elevated levels of p53/p21waf1 mRNA in blood lymphocytes collected before chemotherapy may predict the chemoresponses of lung cancer patients.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, ROC.
Chuen-Ming
CM
Shih
Kwunmin
K
Chen
Yu-Chieh
YC
Wang
Pei-Jung
PJ
Lee
Yi-Ching
YC
Wang
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000627:therapeutic use; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin