Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours

A. Miyanaga, K. Honda, K. Tsuta, M. Masuda, U. Yamaguchi, G. Fujii, A. Miyamoto, S. Shinagawa, N. Miura, H. Tsuda, T. Sakuma, Hisao Asamura, A. Gemma, T. Yamada

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, butno method for predicting their outcome has been established. Materials and methods: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. Results: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine(NE) lung cancers. The expression of variant actinin-4 was significantly associated with poorer overall survival in HGNT patients (P = 0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that the expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients(hazard ratio (HR), 2.15; P = 0.00113) after the presence of lymph node metastasis (HR, 2.25; P = 0.00023). Conclusions: The expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has a high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion.

Original languageEnglish
Article numbermds215
Pages (from-to)84-90
Number of pages7
JournalAnnals of Oncology
Volume24
Issue number1
DOIs
Publication statusPublished - 2013 Jan
Externally publishedYes

Fingerprint

Actinin
Neuroendocrine Tumors
Lung
Lung Neoplasms
Survival
Proportional Hazards Models
Actins
Polymers
Multivariate Analysis
Lymph Nodes
Monoclonal Antibodies
Neoplasm Metastasis
Neoplasms
Proteins

Keywords

  • Actinin-4
  • Alternative splice variant
  • Diagnostic marker
  • High-grade neuroendocrine tumour
  • Prognosis
  • Pulmonary neoplasm

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Miyanaga, A., Honda, K., Tsuta, K., Masuda, M., Yamaguchi, U., Fujii, G., ... Yamada, T. (2013). Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours. Annals of Oncology, 24(1), 84-90. [mds215]. https://doi.org/10.1093/annonc/mds215

Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours. / Miyanaga, A.; Honda, K.; Tsuta, K.; Masuda, M.; Yamaguchi, U.; Fujii, G.; Miyamoto, A.; Shinagawa, S.; Miura, N.; Tsuda, H.; Sakuma, T.; Asamura, Hisao; Gemma, A.; Yamada, T.

In: Annals of Oncology, Vol. 24, No. 1, mds215, 01.2013, p. 84-90.

Research output: Contribution to journalArticle

Miyanaga, A, Honda, K, Tsuta, K, Masuda, M, Yamaguchi, U, Fujii, G, Miyamoto, A, Shinagawa, S, Miura, N, Tsuda, H, Sakuma, T, Asamura, H, Gemma, A & Yamada, T 2013, 'Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours', Annals of Oncology, vol. 24, no. 1, mds215, pp. 84-90. https://doi.org/10.1093/annonc/mds215
Miyanaga, A. ; Honda, K. ; Tsuta, K. ; Masuda, M. ; Yamaguchi, U. ; Fujii, G. ; Miyamoto, A. ; Shinagawa, S. ; Miura, N. ; Tsuda, H. ; Sakuma, T. ; Asamura, Hisao ; Gemma, A. ; Yamada, T. / Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours. In: Annals of Oncology. 2013 ; Vol. 24, No. 1. pp. 84-90.
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AU - Tsuta, K.

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AU - Yamaguchi, U.

AU - Fujii, G.

AU - Miyamoto, A.

AU - Shinagawa, S.

AU - Miura, N.

AU - Tsuda, H.

AU - Sakuma, T.

AU - Asamura, Hisao

AU - Gemma, A.

AU - Yamada, T.

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AB - Background: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, butno method for predicting their outcome has been established. Materials and methods: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. Results: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine(NE) lung cancers. The expression of variant actinin-4 was significantly associated with poorer overall survival in HGNT patients (P = 0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that the expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients(hazard ratio (HR), 2.15; P = 0.00113) after the presence of lymph node metastasis (HR, 2.25; P = 0.00023). Conclusions: The expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has a high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion.

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