Limits...
MicroRNA-155 expression is independently predictive of outcome in chordoma.

Osaka E, Kelly AD, Spentzos D, Choy E, Yang X, Shen JK, Yang P, Mankin HJ, Hornicek FJ, Duan Z - Oncotarget (2015)

Bottom Line: Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction.Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.

View Article: PubMed Central - PubMed

Affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.

ABSTRACT

Background: Chordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma.

Methods: The miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively.

Results: The miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.

Conclusions: We have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.

No MeSH data available.


Related in: MedlinePlus

miR-155 expression is correlated with stage and metastatic potential in chordomaDot-plots showing the relationships between miR-155 expression and (A, B) Enneking stage, and (C) the presence of metastasis. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496207&req=5

Figure 2: miR-155 expression is correlated with stage and metastatic potential in chordomaDot-plots showing the relationships between miR-155 expression and (A, B) Enneking stage, and (C) the presence of metastasis. *p < 0.05.

Mentions: We evaluated the relationships between miR-155 expression levels and clinicopathological features of chordoma patients including gender, age, location, Enneking stage, origin, the presence of local recurrence, and metastasis. In this analysis “primary origin” was defined as those patients who had never received prior treatment for malignant chordoma, and “recurrent origin” was defined as the subset of patients who presented with recurrent disease after surgery at an outside institution. Among the clinical characteristics evaluated, miR-155 expression was significantly correlated with Enneking stage (p = 0.036) and the presence of metastasis (p = 0.035) (Table 1). Interestingly, miR-155 expression levels were positively correlated with disease stage in a step-wise manner, and there were significant differences between Stage 1A + 1B and both Stage 2A + 2B and Stage 3 (p = 0.027, p = 0.031, respectively, Fig. 2A), suggesting that both extent of malignant invasion, and degree of pathologic cellular atypia may be associated with aberrant miR-155 expression. Although there were no statistically significant differences in other clinicopathological features, there was a notable trend for higher miR-155 expression among patients with recurrent disease (Table 1). We also compared quantitative miR-155 expression levels across clinical characteristics and, as expected, we found significant differences associated with Enneking stage (p = 0.006) and the presence of metastasis (p = 0.003) (Fig. 2B, 2C, Supplementary Table S3).


MicroRNA-155 expression is independently predictive of outcome in chordoma.

Osaka E, Kelly AD, Spentzos D, Choy E, Yang X, Shen JK, Yang P, Mankin HJ, Hornicek FJ, Duan Z - Oncotarget (2015)

miR-155 expression is correlated with stage and metastatic potential in chordomaDot-plots showing the relationships between miR-155 expression and (A, B) Enneking stage, and (C) the presence of metastasis. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496207&req=5

Figure 2: miR-155 expression is correlated with stage and metastatic potential in chordomaDot-plots showing the relationships between miR-155 expression and (A, B) Enneking stage, and (C) the presence of metastasis. *p < 0.05.
Mentions: We evaluated the relationships between miR-155 expression levels and clinicopathological features of chordoma patients including gender, age, location, Enneking stage, origin, the presence of local recurrence, and metastasis. In this analysis “primary origin” was defined as those patients who had never received prior treatment for malignant chordoma, and “recurrent origin” was defined as the subset of patients who presented with recurrent disease after surgery at an outside institution. Among the clinical characteristics evaluated, miR-155 expression was significantly correlated with Enneking stage (p = 0.036) and the presence of metastasis (p = 0.035) (Table 1). Interestingly, miR-155 expression levels were positively correlated with disease stage in a step-wise manner, and there were significant differences between Stage 1A + 1B and both Stage 2A + 2B and Stage 3 (p = 0.027, p = 0.031, respectively, Fig. 2A), suggesting that both extent of malignant invasion, and degree of pathologic cellular atypia may be associated with aberrant miR-155 expression. Although there were no statistically significant differences in other clinicopathological features, there was a notable trend for higher miR-155 expression among patients with recurrent disease (Table 1). We also compared quantitative miR-155 expression levels across clinical characteristics and, as expected, we found significant differences associated with Enneking stage (p = 0.006) and the presence of metastasis (p = 0.003) (Fig. 2B, 2C, Supplementary Table S3).

Bottom Line: Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction.Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.

View Article: PubMed Central - PubMed

Affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.

ABSTRACT

Background: Chordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma.

Methods: The miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively.

Results: The miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.

Conclusions: We have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma.

No MeSH data available.


Related in: MedlinePlus