Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas
2018
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.
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