Gene expression identifies heterogeneity of metastatic propensity in high‐grade soft tissue sarcomas

Abstract

BACKGROUND: Metastatic propensity of soft tissue sarcoma (STS) is heterogeneous and may be determined by gene expression patterns that do not correlate well with morphology. The authors have reported gene expression patterns that distinguish 2 broad classes of clear cell renal carcinoma (ccRCC-gene set), and other patterns that can distinguish heterogeneity of serous ovarian carcinoma (OVCA-gene set) and aggressive fibromatosis (AF-gene set); however, clinical follow-up data were not available for these samples. METHODS: In the current study, gene expression patterns in 73 samples of high-grade STS were examined using spotted cDNA microarray slides that contained 16,000 unique UniGene clusters. Approximately 50% of the genes present in the ccRCC-, OVCA-, and AF-gene sets were also represented in the data from this chip set, and these were combined to form a composite gene set of 278 probes. RESULTS: Hierarchical clustering using this composite gene set suggested the existence of subsets of the STS samples. Analysis revealed differences in the time to development of metastatic disease between the clusters defined by the first branch point of the clustering dendrogram (P ¼ .005), and also among the 4 different clusters defined by the second branch points (P ¼ .001). CONCLUSIONS: This approach suggests the existence of >2 subsets of high-grade pleomorphic STS, each with distinct clinical behavior. A composite gene set such as that described here may be useful to stratify STS in clinical trials, and may be of practical utility in patient management. Cancer 2012;118:4235-43.

Microarray analysis of metallothioneins in human diseases—A review

“…Noteworthy, there was no correlation between MT expression and chemoresistance in osteosarcoma [40]. In another study the gene expression of 73 high-grade soft tissue sarcoma samples was analysed by cDNA Microarray and clustered by complete-linkage hierarchical clustering [60]. The ratio of the gene expression in the sample relative to the average signal of expression of all genes examined was determined.…”

“…The ratio of the gene expression in the sample relative to the average signal of expression of all genes examined was determined. Importantly, the samples of patients with the highest rate of metastases were characterized by MT-2A, MT-1X, MT-1F and MT-1H over-expression [60].…”

Gene expression identifies heterogeneity of metastatic behavior among high-grade non-translocation associated soft tissue sarcomas

“…In some cases, gene expression patterns may correlate better with biological behavior than histology, and some studies have suggested that gene expression patterns may correlate with metastatic potential in some high-grade STS [11,12,14,17]. A recent study identified a set of 67 genes involved in mitosis and chromosome integrity, termed the complexity index in sarcomas (CINSARC), that can predict metastasis outcome in non-translocation dependent STS [11] and also synovial sarcoma [18].…”

“…We recently reported the use of a gene set derived from these three studies to separate 73 high grade STS into 2 or 4 groups with different propensity of metastasis [14]. Because the expression data for the STS sample set was limited since it was from a different platform than the Affymetrix system, we pooled the ccRCC-, OVCA-, and AF-gene sets for the earlier study.…”

MicroRNAs in the pathobiology of sarcomas

“…[62][63][64][65] Gene expression profiling has been used to characterize and classify a wide range of sarcomas, in some cases providing a diagnostic resolution more accurate than histological examination. [66][67][68][69][70][71][72] With the advent of high-throughput RNA-Seq, sarcoma researchers are now able to prospectively analyze the differential expression of small RNAs, such as miRNAs, without prior knowledge of their sequence. 73,74 RNA-Seq also allows for the prospective identification of novel genomic rearrangements resulting from gene fusions or premature truncations that may be of particular interest to cancer researchers.…”