Abstract
BackgroundUndifferentiated Pleomorphic Sarcoma (UPS) and high-grade Leiomyosarcoma (LMS) are soft tissue tumors with an aggressive clinical behavior, frequently developing local recurrence and distant metastases. Despite several gene expression studies involving soft tissue sarcomas, the potential to identify molecular markers has been limited, mostly due to small sample size, in-group heterogeneity and absence of detailed clinical data.Materials and MethodsGene expression profiling was performed for 22 LMS and 22 UPS obtained from untreated patients. To assess the relevance of the gene signature, a meta-analysis was performed using five published studies. Four genes (BAD, MYOCD, SRF and SRC) selected from the gene signature, meta-analysis and functional in silico analysis were further validated by quantitative PCR. In addition, protein-protein interaction analysis was applied to validate the data. SRC protein immunolabeling was assessed in 38 UPS and 52 LMS.ResultsWe identified 587 differentially expressed genes between LMS and UPS, of which 193 corroborated with other studies. Cluster analysis of the data failed to discriminate LMS from UPS, although it did reveal a distinct molecular profile for retroperitoneal LMS, which was characterized by the over-expression of smooth muscle-specific genes. Significantly higher levels of expression for BAD, SRC, SRF, and MYOCD were confirmed in LMS when compared with UPS. SRC was the most value discriminator to distinguish both sarcomas and presented the highest number of interaction in the in silico protein-protein analysis. SRC protein labeling showed high specificity and a positive predictive value therefore making it a candidate for use as a diagnostic marker in LMS.ConclusionsRetroperitoneal LMS presented a unique gene signature. SRC is a putative diagnostic marker to differentiate LMS from UPS.
Highlights
Soft Tissue Sarcomas (STS) comprise a heterogeneous group of mesenchymal tumors that represent around 1% of all neoplasms [1,2].Diagnosis of these tumors poses a challenge to the pathologist due to their rarity, pleomorphic nature and histologic overlap with numerous sarcoma subtypes [2]
Higher levels of expression for BAD, SRC, SRF, and MYOCD were confirmed in LMS when compared with Undifferentiated Pleomorphic Sarcoma (UPS)
A distinct molecular profile was demonstrated for LMS-R, mediated by over-expression of genes involved in muscular development and function
Summary
Soft Tissue Sarcomas (STS) comprise a heterogeneous group of mesenchymal tumors that represent around 1% of all neoplasms [1,2]. Diagnosis of these tumors poses a challenge to the pathologist due to their rarity, pleomorphic nature and histologic overlap with numerous sarcoma subtypes [2]. High-grade LMS shows histological similarities to UPS, which can cause difficulties in the distinction between these neoplasms [6]. Undifferentiated Pleomorphic Sarcoma (UPS) and high-grade Leiomyosarcoma (LMS) are soft tissue tumors with an aggressive clinical behavior, frequently developing local recurrence and distant metastases. Despite several gene expression studies involving soft tissue sarcomas, the potential to identify molecular markers has been limited, mostly due to small sample size, in-group heterogeneity and absence of detailed clinical data
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