Abstract

PurposeChordomas are rare, slow-growing sarcomas without any accepted prognostic biomarkers. Owing to their proximity to critical neurovascular structures, discovering predictive biomarkers in chordoma has been a significant research effort because it may potentially reduce risky therapies in patients with less aggressive tumors. In response, because cyclin E1 overexpression correlates with patient prognosis in several malignancies, we investigated its expression in chordoma and whether it informs patient prognosis.MethodsSeventy-five chordoma patient specimens were enrolled in a tissue microarray (TMA) to evaluate cyclin E1 expression via immunohistochemical staining. Western blot was used to assess cyclin E1 expression in chordoma cell lines and fresh tissues. We then correlated cyclin E1 staining intensity in the TMA to clinicopathological features and chordoma patient outcomes.ResultsSixty-three percent of the chordoma patient specimens in the TMA, fifty-six percent of the fresh chordoma tissues, and all chordoma cell lines showed high cyclin E1 expression. In TMA analysis, cyclin E1 expression positively correlated to chordoma patient disease status. By survival analysis, high cyclin E1 expression was an independent prognostic risk factor for chordoma patients along with advanced disease status and positive surgical margin.ConclusionCyclin E1 is a promising biomarker predicting chordoma patient prognosis.

Highlights

  • Chordomas are rare bone sarcomas that arise from the transformed remnants of notochord, with an incidence of 0.1/ 100,000 people per year [1]

  • In tissue microarray (TMA) analysis, cyclin E1 expression positively correlated to chordoma patient disease status

  • Clinicopathological Characteristics of 75 Chordoma Patients Enrolled in TMA

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Summary

Introduction

Chordomas are rare bone sarcomas that arise from the transformed remnants of notochord, with an incidence of 0.1/ 100,000 people per year [1]. The 5-year survival rate for chordoma patients is an optimistic 70-81%, local recurrence and subsequent metastasis occurs approximately half the time after surgery, with no systemic therapies having shown major benefit [1, 5, 6]. While their diagnosis is made according to clinicopathological features and brachyury expression which is a prominent transcription factor in notochord development, brachyury is a diagnostic biomarker and therapeutic target rather than a prognostic biomarker [7,8,9,10]. There is, an urgent need for the identification of chordoma biomarkers to better ascertain patient prognosis and whether high-risk surgeries or adjuvant therapies are indicated

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