Yuan-Ting Lee

Bio: Yuan-Ting Lee is an academic researcher from Chang Gung University. The author has contributed to research in topics: Metastasis & Tumor progression. The author has an hindex of 1, co-authored 1 publications receiving 34 citations.

Prognostic Implication of Ezrin Overexpression in Myxofibrosarcomas

Abstract: Background The bases of tumorigenesis, progression, and metastasis remain obscure in myxofibrosarcoma. As a member of ezrin-radixin-moesin family, ezrin acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion–mediated signaling. It is implicated in tumor progression and metastatic dissemination, and it is associated with adverse outcomes in several cancer types, including pediatric sarcomas.

ASS1 as a Novel Tumor Suppressor Gene in Myxofibrosarcomas: Aberrant Loss via Epigenetic DNA Methylation Confers Aggressive Phenotypes, Negative Prognostic Impact, and Therapeutic Relevance

Abstract: Purpose: The principal goals were to identify and validate targetable metabolic drivers relevant to myxofibrosarcoma pathogenesis using a published transcriptome. Experimental Design: As the most significantly downregulated gene regulating amino acid metabolism, argininosuccinate synthetase ( ASS1) was selected for further analysis by methylation-specific PCR, pyrosequencing, and immunohistochemistry of myxofibrosarcoma samples. The roles of ASS1 in tumorigenesis and the therapeutic relevance of the arginine-depriving agent pegylated arginine deiminase (ADI-PEG20) were elucidated in ASS1-deficient myxofibrosarcoma cell lines and xenografts with and without stable ASS1 reexpression. Results: ASS1 promoter hypermethylation was detected in myxofibrosarcoma samples and cell lines and was strongly linked to ASS1 protein deficiency. The latter correlated with increased tumor grade and stage and independently predicted a worse survival. ASS1-deficient cell lines were auxotrophic for arginine and susceptible to ADI-PEG20 treatment, with dose-dependent reductions in cell viability and tumor growth attributable to cell-cycle arrest in the S-phase. ASS1 expression was restored in 2 of 3 ASS1-deficient myxofibrosarcoma cell lines by 5-aza-2′-deoxycytidine, abrogating the inhibitory effect of ADI-PEG20. Conditioned media following ASS1 reexpression attenuated HUVEC tube-forming capability, which was associated with suppression of MMP-9 and an antiangiogenic effect in corresponding myxofibrosarcoma xenografts. In addition to delayed wound closure and fewer invading cells in a Matrigel assay, ASS1 reexpression reduced tumor cell proliferation, induced G 1 -phase arrest, and downregulated cyclin E with corresponding growth inhibition in soft agar and xenograft assays. Conclusions: Our findings highlight ASS1 as a novel tumor suppressor in myxofibrosarcomas, with loss of expression linked to promoter methylation, clinical aggressiveness, and sensitivity to ADI-PEG20. Clin Cancer Res; 19(11); 2861–72. ©2013 AACR .

Expression of ezrin correlates with malignant phenotype of lung cancer, and in vitro knockdown of ezrin reverses the aggressive biological behavior of lung cancer cells

Abstract: Ezrin, one of the ezrin–radixin–moesin proteins, is involved in the formation of cell membrane processes such as lamellipodia and filopodia and acts as a membrane–cytoskeleton linker. Its aberrant expression correlates with development and progression of several human cancers. However, the expression of ezrin and its role in lung cancer are currently unknown. In this study, we performed ezrin small interfering RNA transfection in two lung cancer cell lines and examined the effects on malignant phenotypes in cancer cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and chamber transwell assays. Ezrin knockdown significantly reduced the proliferation, migration, and invasion of lung cancer cells in vitro. To address the possible mechanisms, we evaluated the expression of adhesion molecules E-cadherin and β-catenin by Western blot and reverse transcriptase-polymerase chain reaction analyses. The results demonstrated that downregulation of ezrin reduced β-catenin and increased E-cadherin at the protein level but had no effects on their mRNA levels, suggesting posttranscriptional regulation of these two adhesion molecules. Immunofluorescence assays revealed that ezrin knockdown restored membranous expression of E-cadherin and decreased cytoplasmic β-catenin in lung cancer cells. In addition, ezrin expression was immunohistochemically evaluated on 135 normal and 183 lung cancer tissues. The expression of ezrin was significantly higher in cancer samples than paired autologous normal lung tissues. In normal bronchial epithelium, ezrin was mainly localized on the apical membrane, while in lung cancers and metastatic foci, ezrin was primarily distributed in cytoplasm. Among lung cancer tissues, expression of ezrin was higher in the invasive front of primary lesions and the highest in lymphatic metastasis. Statistical analysis demonstrated that ezrin expression correlated significantly with lymphatic metastasis and advanced TNM stage. Our data suggest that ezrin may play a crucial role in governing the biological behavior of lung cancer.

Integrated genetic and epigenetic analysis of myxofibrosarcoma

Abstract: Myxofibrosarcoma (MFS) is a common adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high local recurrence rate. Here we report the genetic and epigenetic landscape of MFS based on the results of whole-exome sequencing (N = 41), RNA sequencing (N = 29), and methylation analysis (N = 41), using 41 MFSs as a discovery set, and subsequent targeted sequencing of 140 genes in the entire cohort of 99 MFSs and 17 MFSs' data from TCGA. Fourteen driver genes are identified, including potentially actionable therapeutic targets seen in 37% of cases. There are frequent alterations in p53 signaling (51%) and cell cycle checkpoint genes (43%). Other conceivably actionable driver genes including ATRX, JAK1, NF1, NTRK1, and novel oncogenic BRAF fusion gene are identified. Methylation patterns cluster into three subtypes associated with unique combinations of driver mutations, clinical outcomes, and immune cell compositions. Our results provide a valuable genomic resource to enable the design of precision medicine for MFS.

Prognostic Value of Ezrin in Various Cancers: A Systematic Review and Updated Meta-analysis.

Abstract: More and more studies have investigated the effects of Ezrin expression level on the prognostic role in various tumors. However, the results remain controversial rather than conclusive. Here, we performed a systematic review and meta-analysis to evaluate the correlation of Ezrin expression with the prognosis in various tumors. the pooled hazard ratios (HR) with the corresponding 95% confidence intervals (95% CI) were calculated to evaluate the degree of the association. The overall results of fifty-five studies with 6675 patients showed that elevated Ezrin expression was associated with a worse prognosis in patients with cancers, with the pooled HRs of 1.86 (95% CI: 1.51-2.31, P < 0.001) for over survival (OS), 2.55 (95% CI: 2.14-3.05, P < 0.001) for disease-specific survival (DFS) and 2.02 (95% CI: 1.13-3.63, P = 0.018) for disease-specific survival (DSS)/metastasis-free survival (MFS) by the random, fixed and random effect model respectively. Similar results were also observed in the stratified analyses by tumor types, ethnicity background and sample source. This meta-analysis suggests that Ezrin may be a potential prognostic marker in cancer patients. High Ezrin is associated with a poor prognosis in a variety of solid tumors.