Efficacy of adjuvant chemotherapy for non-small cell lung cancer assessed by metastatic potential associated with ACTN4.
Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ).In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR.10, which was a clinical trial to probe the clinical benefits of ADJ in stage-IB/II patients with NSCLC. The patients who were enrolled by JBR.10 were classified into 2 subgroups according to expression of the ACTN4 transcript: ACTN4 positive (ACTN4 (+)) and ACTN4 negative (ACTN4 (-)). In the ACTN4 (+) group, overall survival (OS) was significantly higher in the ADJ subgroup compared with the observation subgroup (OBS), indicating a significant survival benefit of ADJ. However, no difference in OS was found between ADJ and OBS groups in ACTN4 (-). Although ACTN4 expression level did not correlate with the chemosensitivity of cancer cell lines for cytotoxic drugs, the metastatic potential of A549 lung adenocarcinoma cells was significantly reduced by ACTN4 shRNA in in vitro assays and in an animal transplantation model. The clinical and preclinical data suggested that ACTN4 is a potential predictive biomarker for efficacy of ADJ in stage-IB/II patients with NSCLC, by reflecting the metastatic potential of tumor cells.
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Nami
N
Miura
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Masahiro
M
Kamita
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Takanori
T
Kakuya
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Yutaka
Y
Fujiwara
Division of Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Koji
K
Tsuta
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Hideaki
H
Shiraishi
Department of Functional Analysis, Fundamental Innovative Oncology Core Center, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Fumitaka
F
Takeshita
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Takahiro
T
Ochiya
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Hirokazu
H
Shoji
Abnova, Taipei 114, Taiwan.
Wilber
W
Huang
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Yuichiro
Y
Ohe
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Tesshi
T
Yamada
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan.|Japan Agency for Medical Research and Development: AMED-CREST, AMED, Tokyo 100-0004, Japan.
Kazufumi
K
Honda
D000072283:A549 Cells; D000185:Actinin / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D002465:Cell Movement / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011013:Pneumonectomy; D016016:Proportional Hazards Models; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
C111453:ACTN4 protein, human; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000185:Actinin
ACTN4 (actinin-4); JBR.10; early stage of non-small cell lung cancer (NSCLC); predictive biomarker for adjuvant chemotherapy