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Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas

Oncogene volume 30, pages 4015–4025 (2011)Cite this article

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Abstract

Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) as a candidate for a metastasis-predicting marker from the gene expression profiles of 65 spindle cell sarcomas. A multivariate analysis determined that AFAP1L1 was an independent factor for predicting the occurrence of distant metastasis (P=0.0001), which was further confirmed in another set of 41 tumors by a quantitative mRNA expression analysis. Immunohistochemical staining using paraffin-embedded tumor tissues revealed that the metastasis-free rate was significantly better in tumors negative for AFAP1L1 (P=0.0093 by log-rank test). Knocking down the AFAP1L1 gene in sarcoma cells resulted in inhibition of the cell invasion, and forced expression of AFAP1L1 in immortalized human mesenchymal stem cells induced anchorage-independent growth and increased cell invasiveness with high activity levels of matrix metallopeptidase. Furthermore, tumor growth in vivo was accelerated in AFAP1L1-transduced sarcoma cell lines. These results suggest that AFAP1L1 has a role in the progression of spindle cell sarcomas and is a prognostic biomarker.

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Acknowledgements

We thank Drs H Sonobe, A Kawai, S Tanaka, O Larsson, A Ogose, and H Kanda for providing cell lines, and T Tsunoda and S Miyano for data analyses. This work was supported by Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology.

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Author notes

  1. T Katagiri

    Present address: Current address: Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Japan.,

  2. M Furu and Y Kajita: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

    M Furu, Y Kajita, T Ishibe, Y Shima, K Nishijo, D Uejima, R Takahashi, T Aoyama & J Toguchida

  2. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    M Furu, T Ishibe, Y Shima, K Nishijo, T Nakayama, T Nakamura & J Toguchida

  3. Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Y Kajita

  4. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    S Nagayama & R Takahashi

  5. Department of Orthopaedic Surgery, Kansai Medical University, Osaka, Japan

    D Uejima & T Aoyama

  6. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan

    Y Nakashima

  7. Department of Genomic Medical Sciences, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    M Ikegawa

  8. Laboratory for DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Kyoto, Japan

    S Imoto

  9. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Kyoto, Japan

    T Katagiri & Y Nakamura

  10. Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan

    J Toguchida

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Correspondence to J Toguchida.

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Furu, M., Kajita, Y., Nagayama, S. et al. Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas. Oncogene 30, 4015–4025 (2011). https://doi.org/10.1038/onc.2011.108

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