Gene Expression Profiling of Desmoid Tumors by cDNA Microarrays and Correlation with Progression-Free Survival

Abstract

Purpose: Because desmoid tumors exhibit an unpredictable clinical course, translational research is crucial to identify the predictive factors of progression in addition to the clinical parameters. The main issue is to detect patients who are at a higher risk of progression. The aim of this work was to identify molecular markers that can predict progression-free survival (PFS).Experimental Design: Gene-expression screening was conducted on 115 available independent untreated primary desmoid tumors using cDNA microarray. We established a prognostic gene-expression signature composed of 36 genes. To test robustness, we randomly generated 1,000 36-gene signatures and compared their outcome association to our define 36-genes molecular signature and we calculated positive predictive value (PPV) and negative predictive value (NPV).Results: Multivariate analysis showed that our molecular signature had a significant impact on PFS while no clinical factor had any prognostic value. Among the 1,000 random signatures generated, 56.7% were significant and none was more significant than our 36-gene molecular signature. PPV and NPV were high (75.58% and 81.82%, respectively). Finally, the top two genes downregulated in no-recurrence were FECH and STOML2 and the top gene upregulated in no-recurrence was TRIP6.Conclusions: By analyzing expression profiles, we have identified a gene-expression signature that is able to predict PFS. This tool may be useful for prospective clinical studies.

5-ALA fluorescence of cerebral metastases and its impact for the local-in-brain progression

“…However, heterogeneity of cerebral metastases with the same histology and origin is well known [39–41]. Several molecular markers, e.g.…”

A Mesenteric Desmoid Tumor with Rapid Progression

“…A CTNNB1 (the gene encoding β-catenin) 45F mutation, low-intensity β-catenin nuclear staining, and increased midkine expression are significantly correlated with increased recurrence in cases of sporadic DT (12,13). Recently, a prognostic gene expression signature composed of 36 genes that can predict progression-free survival in DT has been established (14). In the future, patients with these high-risk conditions may especially benefit from adjuvant therapeutic approaches.…”

Adult desmoid tumors: biology, management and ongoing trials

“…Several studies suggest that the S45F CTNNB1 mutation is an important risk factor for local recurrence after curative-intent surgery for primary desmoid tumor (Table 1) [25–29]. Salas et al [30] developed a 36-gene molecular signature that predicted relapse after surgery with an accuracy of 78%. In this model, the top two genes that were upregulated in the recurrence group were FECH ( ferrochelatase, which is involved in protoheme biosynthesis) and stomatin-like protein 2, which regulates mitochondrial functions.…”

“…Other parameters included in the multivariate models: young age [30]; sex, R0 resection, tumor size, and tumor location [27]; no other significant prognosticator [27]. …”