Background: The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies.
Materials-methods: SDP35/DEPDC1A and XTP1/DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox's regression analyses.
Results: SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors.
Conclusions: Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis.