Elevated p53 and p21waf1 mRNA expression in blood lymphocytes from lung cancer patients with chemoresistance

Cancer Detect Prev. 2007;31(5):366-70. doi: 10.1016/j.cdp.2007.10.003. Epub 2007 Nov 26.

Abstract

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.

Conclusion: Our results suggest that elevated levels of p53/p21waf1 mRNA in blood lymphocytes collected before chemotherapy may predict the chemoresponses of lung cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cisplatin / therapeutic use
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
  • Drug Resistance, Neoplasm / genetics*
  • Genes, p53 / genetics
  • Genes, p53 / radiation effects
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lymphocytes / metabolism*
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Cisplatin