Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas.

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.

Activity of rheumatoid arthritis and urinary pyridinoline and deoxypyridinoline.

The aims of this study were to examine levels of the crosslinking components of collagen, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) which are bone resorption markers, in patients with rheumatoid arthritis (RA), and to determine their association with disease activity and bone mineral density (BMD). These bone resorption markers were measured in 35 postmenopausal women with RA, 30 age-matched female patients with osteoarthritis of the knee (controls), and 47 patients with bone fracture. The mean BMD in the RA patients was lower than that in the control group, and the Z-score (number of standard deviations above and below the normal mean after comparison with age and sex matched normal control values) was significantly lower. Mean levels of Pyr and D-Pyr were significantly higher in the RA patients than in the control group, and the Pyr/D-Pyr ratio was also higher in the RA patients than in the other groups. Regarding the relationship between the bone resorption markers and RA activity, Pyr increased as the Lansbury's joint score (number of swollen joints corrected for joint size according Lansbury) rose, showing a normal correlation; D-Pyr also showed a normal correlation. Pyr and D-Pyr were high in patients with a high erythrocyte sedimentation rate, showing a normal correlation. Only Pyr increased with increases in C-reactive protein (CRP), showing a normal correlation. These findings suggested that a high value for Pyr (which includes a large amount of collagen type II) indicated that RA activity was affected more by synovitis, rather than by systemic osteoporosis.