Abstract
Chordoma is a rare bone cancer originating from embryologic notochordal remnants. Clival chordomas show different dural penetration ability, with serious dural penetration exhibiting poorer prognosis. The molecular mechanism of dural penetration is not clear. We analyzed lncRNA and mRNA profiles in 12 chordoma patients with different degrees of dural penetration using expression microarrays. The differentially expressed lncRNAs and mRNAs were used to construct a lncRNA-mRNA co-expression network. LncRNAs were classified into lincRNA, enhancer-like lncRNA, or antisense lncRNA. Biological functions for lncRNAs were predicted according to the lncRNA-mRNA network and adjacent coding genes by pathway analysis. The 2760 lncRNAs and 3988 mRNAs were differentially expressed in chordomas between two groups of patients with and without dural penetration. Possible pathway involvement of the significance among the 55 lncRNAs located in the lncRNA-mRNA network, 24 lincRNAs, 7 enhancer-like lncRNAs, and 14 antisense lncRNAs include cell adhesion, metastasis, invasion, proliferation, and apoptosis. Expression of 10 lncRNAs and mRNAs, and epidermal growth factor mRNA with two identified lncRNAs were subsequently verified by qRT-PCR in chordoma tissues. Our report predicts the biological functions of many lncRNAs which may be used as diagnostic and prognostic biomarkers as well as therapeutic targets during the process of dural penetration in chordoma.
Highlights
Chordomas are rare, malignant, primary bone tumors, with an incidence of approximately 0.1/100,000/year [1]
We identified differentially expressed Long non-coding RNAs (lncRNAs) and gene expression profiles of chordomas with varying degrees of dural penetration and constructed lncRNA-gene co-expression networks to reveal the functional role of lncRNAs in regulating dural penetration of clivus chordoma
In the chordomas samples with serious dural penetration, a bulge from the tumor into intracranial areas could be found in magnetic resonance imaging (MRI), whereas dural perforation was found during the operation (Figure 1C, 1D)
Summary
Malignant, primary bone tumors, with an incidence of approximately 0.1/100,000/year [1]. They originate from remnants of the embryologic notochord, with the most common sites being the sacrum (50-60%), clivus region of the skull base (25-35%), and cervical and thoracolumbar vertebrae (15%) [2]. The standard treatment for chordoma is maximum surgical resection. Local recurrence and metastasis can occur after surgical resection, and current radiotherapy and chemotherapeutic protocols are largely ineffective [3,4,5]. Some tumors severely penetrate the dura mater, with little bone invasion, while others show little or no dura mater penetration with extensive skull base bone invasion. Our previous study showed chordoma patients with serious dural penetration have poorer prognosis and patients without dural penetration have longer overall survival and progressive-free survival [10]
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