Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker

Int J Cancer. 2005 Nov 10;117(3):460-8. doi: 10.1002/ijc.21172.

Abstract

Cisplatin-based (CDDP-based) adjuvant chemotherapy of non-small cell lung cancer (NSCLC) was reported to yield 5-15% improvement in 5-year survival compared to complete resection alone. The importance of information concerning preselection of good responders has become increasingly evident. The purpose of our study is the establishment of a preselection of good responders for CDDP-based adjuvant chemotherapy. We investigated protein expressions comparing intensity between parent strains (H69 and PC14 lung cancer cultured cells) and resistant strains against CDDP using 2-dimensional polyacrylamide gel electrophoresis (2-DE). Immunohistochemically, we evaluated the relationship between protein expression associated with CDDP-resistance and the clinical effects of platinum-based postoperative adjuvant chemotherapy using 126 surgically-resected NCLC materials. We detected 2 kinds of polypeptides that changed expression levels on 2-DE gels. The analyses of the amino acid sequence showed that these polypeptides were reticulocalbin (RCN) and glutathione-S-transferase-pi (GST-pi). The 2-DE analysis showed decreased expression in RCN and overexpression in GST-pi with the acquisition of CDDP-drug resistance. RCN-transfectant of H69 CDDP-resistant strain showed intermediate sensitivity between the parent strain and the CDDP-resistant strain. RCN-positive cases showed a statistically significant better disease-free survival only in the cases receiving postoperative platinum-based adjuvant chemotherapy after curative resection (p = 0.007). In addition, cases that were both RCN-positive and GST-pi-negative showed a statistically significantly better outcome (p = 0.0150). In the cases without postoperative adjuvant chemotherapy no relationship between the outcome and these expressions was seen. The evaluation of RCN and GST-pi might provide valuable information concerning postoperatively therapeutic strategy from the standpoint of individualized postoperative therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biomarkers, Tumor
  • Calcium-Binding Proteins / genetics*
  • Cancer Vaccines
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemotherapy, Adjuvant
  • Cisplatin / toxicity
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Glutathione S-Transferase pi
  • Glutathione Transferase / genetics*
  • Humans
  • Isoenzymes / genetics*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Transfection

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Cancer Vaccines
  • DNA, Complementary
  • Isoenzymes
  • Peptide Fragments
  • reticulocalbin
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Cisplatin