Periostin and Epithelial–Mesenchymal Transition Score as Novel Prognostic Markers for Leiomyosarcoma, Myxofibrosarcoma, and Undifferentiated Pleomorphic Sarcoma

Abstract

Interpatient clinical variability in soft-tissue sarcomas (STS) highlights the need for novel prognostic markers supporting patient risk stratification. As sarcomas might exhibit a more mesenchymal or a more epithelial state, we focused on epithelialmesenchymal and mesenchymal-epithelial transitions (EMT/ MET) for prognostic clues, and selected three histotypes with variable aggressiveness.Experimental Design: The expression of EMT/MET-related factors was measured by qRT-PCR in 55 tumor samples from patients with leiomyosarcoma, myxofibrosarcoma, or undifferentiated pleomorphic sarcoma. The identified marker was further evaluated by IHC in 31 leiomyosarcomas and by measuring its circulating levels in 67 patients. The prognostic value of a sarcomatailored EMT score was analyzed. Epirubicin chemosensitivity and migration were studied in primary STS cultures. Associations with overall survival (OS) were assessed using Kaplan-Meier and Cox regression methods.Results: High expression of periostin, a mesenchymal matricellular protein, in sarcoma tissues (P ¼ 0.0024), its high stromal accumulation in leiomyosarcomas (P ¼ 0.0075), and increased circulation (>20 ng/mL, P ¼ 0.0008) were associated with reduced OS. High periostin expression [HR 2.9; 95% confidence interval (CI), 1.3-6.9; P ¼ 0.0134] and circulation (HR 2.6; 95% CI, 1.3-5.1; P ¼ 0.0086), and a mesenchymal EMT score (mesenchymal vs. transitioning; HR, 5.2; 95% CI, 2.1-13.0, P ¼ 0.0005) were associated with increased risk in multivariable models. An intrinsic or induced mesenchymal state enhanced chemoresistance and migration in sarcoma cell lines.Conclusions: Although limited to a pilot study, these findings suggest that periostin might contribute prognostic information in the three studied STS histotypes. Moreover, a transitioning EMT score measured in the tumor might predict a less active and a more chemosensitive disease.

Exogenous Thyroid Hormone Is Associated with Shortened Survival and Upregulation of High-Risk Gene Expression Profiles in Steroid Receptor–Positive Breast Cancers

“…A corresponding linked database was constructed with IRB approval, including clinical history, hormonal therapy including THRT use, surgical, radiologic, and drug treatment, pathology data, recurrence sites and dates, and outcomes. A REMARK flow diagram of breast cancer samples and analyses are shown in Figure 1A (27).…”

“…A REMARK flow diagram of the patients and the observational study is shown Fig. 1A (27). The majority of patients were treated with only surgery (usually a modified radical mastectomy, as was the practice at that time) and were systemically treatment naïve, with tamoxifen given to 111/820 (13.5%) and chemotherapy administered to 64/820 (7.8%).…”

CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway

“…The IHC score was measured as follows: (1) staining area score: 0, <5%; 1, 5–25%; 2, 25–50%; 3, 50–75%; and 4, > 70%; (2) staining intensity score: 0, no staining; 1, weak staining; 2, moderate staining; and 3, intense staining; and (3) total staining score was estimated through staining intensity and staining area. Samples with a score ≥6 were considered to indicate high expression, while those with a score <6 were considered to have low expression [ 27 ].…”

Mechanisms Involved in the Promoting Activity of Fibroblasts in HTLV-1-Mediated Lymphomagenesis: Insights into the Plasticity of Lymphomatous Cells

“…RNA concentration and purity were measured as described above. The expression of genes linked to a mesenchymal state ( SNAI1 , SNAI2 , ZEB1 , SIP1 , α-SMA and CDH2 / N-cadherin ) and stemness ( NANOG and OCT4 ) was assessed by quantitative real-time PCR (qRT-PCR), as previously reported [ 73 ]. Primer sets used in qRT-PCR were previously published [ 73 , 74 , 75 ].…”

“…The expression of genes linked to a mesenchymal state ( SNAI1 , SNAI2 , ZEB1 , SIP1 , α-SMA and CDH2 / N-cadherin ) and stemness ( NANOG and OCT4 ) was assessed by quantitative real-time PCR (qRT-PCR), as previously reported [ 73 ]. Primer sets used in qRT-PCR were previously published [ 73 , 74 , 75 ]. The expression levels of analysed genes are reported as a relative quantification calculated using the human porphobilinogen deaminase gene as the endogenous control with the 2 −ΔΔCt method [ 76 ].…”