Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas.
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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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| Authors | M Furu, Y Kajita, S Nagayama, T Ishibe, Y Shima, K Nishijo, D Uejima, R Takahashi, T Aoyama, T Nakayama, T Nakamura, Y Nakashima, M Ikegawa, S Imoto, T Katagiri, Y Nakamura, J Toguchida |
| Journal | Oncogene (Oncogene) Vol. 30 Issue 38 Pg. 4015-25 (Sep 22 2011) ISSN: 1476-5594 [Electronic] England |
| PMID | 21516130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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