title: Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas.
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.
authors.affiliation: Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Furu
authors.forename: Y
authors.initials: Y
authors.lastname: Kajita
authors.forename: S
authors.initials: S
authors.lastname: Nagayama
authors.forename: T
authors.initials: T
authors.lastname: Ishibe
authors.forename: Y
authors.initials: Y
authors.lastname: Shima
authors.forename: K
authors.initials: K
authors.lastname: Nishijo
authors.forename: D
authors.initials: D
authors.lastname: Uejima
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Ikegawa
authors.forename: S
authors.initials: S
authors.lastname: Imoto
authors.forename: T
authors.initials: T
authors.lastname: Katagiri
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Toguchida
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014408:Biomarkers, Tumor; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D012509:Sarcoma / Q000235:genetics / Q000473:pathology*
chemical_list: C559217:AFAP1L1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D020780:Matrix Metalloproteinase 9