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远上游元件结合蛋白1的表达与骶骨脊索瘤中c-Myc的表达相关,并与肿瘤进展和不良预后相关。

Expression of far upstream element-binding protein 1 correlates with c-Myc expression in sacral chordomas and is associated with tumor progression and poor prognosis.

作者信息

Wen Hai, Ma Hong, Li Pengzhi, Zheng Jiaoyun, Yu Yipin, Lv Guohua

机构信息

Department of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China.

Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha 410011, China.

出版信息

Biochem Biophys Res Commun. 2017 Sep 30;491(4):1047-1054. doi: 10.1016/j.bbrc.2017.08.008. Epub 2017 Aug 3.

DOI:10.1016/j.bbrc.2017.08.008
PMID:28780352
Abstract

The far upstream element (FUSE)-binding protein 1 (FUBP1), a well-known transcriptional regulator of the proto-oncogene c-Myc, has been demonstrated by previous work to be aberrantly expressed in a variety of tumors and plays a critical role in tumor progression; however, its expression and function in relatively rare and aggressive chordomas remains unclear. In this retrospective study, we reviewed clinicopathologic characteristics of 40 patients diagnosed with sacral chordoma, and analyzed 40 tumor and 20 distant normal tissues obtained from patients during the primary surgical tumor excision. Using immunohistochemistry, we observed an up-regulation in the expression of FUBP1 and c-Myc in sacral chordomas compared with the normal tissues (P = 0.001 for both). Additionally, positive correlations of FUBP1 expression with c-Myc (γ = 0.651, P < 0.001) and the cell proliferation index Ki-67 expression (γ = 0.447, P = 0.004) were indicated using Spearman's rank correlation coefficient. Increased expression of FUBP1 was significantly associated with tumor invasion into the surrounding muscles (P = 0.002). Kaplan-Meier curves demonstrated the association between FUBP1 levels and the patients' local recurrence-free survival (LRFS) (P < 0.001) but not with the overall survival (OS) (P = 0.070). The independent prognostic significance of FUBP1 levels for the LRFS was indicated by multivariate analysis (HR = 4.272; 95% CI, 1.133-16.112; P = 0.032). Our findings demonstrate an association between FUBP1 levels and chordoma progression and prognosis, suggesting that FUBP1 can be used as a biomarker and a potential therapeutic target.

摘要

远上游元件(FUSE)结合蛋白1(FUBP1)是原癌基因c-Myc的一种著名转录调节因子,先前的研究表明其在多种肿瘤中异常表达,并在肿瘤进展中起关键作用;然而,其在相对罕见且侵袭性强的脊索瘤中的表达和功能仍不清楚。在这项回顾性研究中,我们回顾了40例诊断为骶骨脊索瘤患者的临床病理特征,并分析了在初次手术切除肿瘤时从患者身上获取的40个肿瘤组织和20个远处正常组织。通过免疫组织化学,我们观察到与正常组织相比,骶骨脊索瘤中FUBP1和c-Myc的表达上调(两者P值均为0.001)。此外,使用Spearman等级相关系数表明FUBP1表达与c-Myc(γ = 0.651,P < 0.001)以及细胞增殖指数Ki-67表达(γ = 0.447,P = 0.004)呈正相关。FUBP1表达增加与肿瘤侵犯周围肌肉显著相关(P = 0.002)。Kaplan-Meier曲线显示FUBP1水平与患者的局部无复发生存期(LRFS)相关(P < 0.001),但与总生存期(OS)无关(P = 0.070)。多因素分析表明FUBP1水平对LRFS具有独立的预后意义(HR = 4.272;95%CI,1.133 - 16.112;P = 0.032)。我们的研究结果表明FUBP1水平与脊索瘤进展和预后之间存在关联,提示FUBP1可作为一种生物标志物和潜在的治疗靶点。

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