Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker.
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.
Hirano
Takashi
T
Department of Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan. thirano@tokyo-med.ac.jp
Kato
Harubumi
H
Maeda
Masahiro
M
Gong
Yunbo
Y
Shou
Yanning
Y
Nakamura
Miho
M
Maeda
Junichi
J
Yashima
Koichi
K
Kato
Yasufumi
Y
Akimoto
Shingo
S
Ohira
Tatsuo
T
Tsuboi
Masahiro
M
Ikeda
Norihiko
N
D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins / Q000235:genetics*; D019496:Cancer Vaccines; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000633:toxicity; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D014162:Transfection
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D019496:Cancer Vaccines; D018076:DNA, Complementary; D007527:Isoenzymes; D010446:Peptide Fragments; C078865:reticulocalbin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D002945:Cisplatin