Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification

R. Noro, K. Honda, K. Tsuta, G. Ishii, A. M. Maeshima, N. Miura, K. Furuta, T. Shibata, H. Tsuda, A. Ochiai, T. Sakuma, N. Nishijima, A. Gemma, H. Asamura, K. Nagai, T. Yamada

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


Background: Even if detected at an early stage, a substantial number of lung cancers relapse after curative surgery. However, no method for distinguishing such tumors has yet been established. Patients and methods: The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically resected adenocarcinomas of the lung. Results: Amplification (an increase in the copy number by =2.0 fold) of the ACTN4 gene was detected in two of seven lung adenocarcinoma cell lines and 79 (15%) of 543 cases of pathological stage I-IV lung adenocarcinoma. Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death (hazard ratio, 6.78; P = 9.48 × 10-5, Cox regression analysis) among 290 patients with stage I lung adenocarcinoma. The prognostic significance of ACTN gene amplification was further validated in three independent cohorts totaling 1033 patients. Conclusions: Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.

Original languageEnglish
Pages (from-to)2594-2600
Number of pages7
JournalAnnals of Oncology
Issue number10
Publication statusPublished - 2013 Oct
Externally publishedYes


  • Actinin-4 (ACTN4)
  • Biomarker
  • Gene amplification
  • Lung neoplasm
  • Prognosis

ASJC Scopus subject areas

  • Hematology
  • Oncology


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