SPHK1在骶骨脊索瘤中的表达及其与MAPK通路的相关性研究

发布时间：2018-03-07 09:23

本文选题：骶骨脊索瘤　切入点：SPHK1　出处：《苏州大学》2015年硕士论文　论文类型：学位论文

【摘要】：第一部分SPHK1在骶骨脊索瘤中的表达及其与预后的相关性目的:骶骨脊索瘤是一种容易局部复发的原发性恶性骨肿瘤。由于其对于传统的化疗和放疗不敏感,手术切除仍然是首选的治疗手段。然而,即使手术完整切除肿瘤,其复发率仍然较高。目前,研究者们已经在研究生物标志物和治疗靶点方面投入了较多的精力,但是肿瘤行为的分子机制仍然不清楚。本研究旨在研究SPHK1在骶骨脊索瘤中的表达及其临床意义,为脊索瘤的预后判断及分子靶向治疗提供参考依据。方法:在本研究中,我们通过免疫组化染色和实时定量RT-PCR的方法测定了42例骶骨脊索瘤和16例瘤旁正常组织标本中的鞘氨醇激酶1(SPHK1)的表达情况。并且进一步分析了SPHK1与临床因素及患者预后之间的关系。结果:免疫组化结果显示42例骶骨脊索瘤组织标本中,69%(29/42)呈现SPHK1高表达,而在瘤旁正常组织,只有19%(3/16)高表达(P=0.001)。同时,q RT-PCR结果也显示了骶骨脊索瘤中SPHK1 m RNA水平明显高于瘤旁正常组织(P0.05)。卡方检验结果显示SPHK1高表达与肿瘤的复发和周围肌肉侵袭相关(P=0.019,P=0.005),而与患者的性别、年龄、肿瘤的生长部位和大小无关(P0.05)。生存分析结果表明SPHK1高表达患者持续无瘤生存时间短于SPHK1低表达患者。结论:本研究发现SPHK1的m RNA和蛋白在脊索瘤中都呈过表达,与骶骨脊索瘤的侵袭和复发明显相关,它有望作为一个脊索瘤的生物学标志物和治疗靶点。第二部分SPHK1在骶骨脊索瘤中的表达与MAPK通路的相关性目的:脊索瘤是一种少见的来源于胚胎残余脊索组织的恶性骨肿瘤。研究表明SPHK1能够调节MAPK通路来促进肿瘤的发生与发展。文献报道,MAPK通路参与了恶性肿瘤的发生与进展,而其中成员RAF-1和ERK1/2作用显著。本研究旨在检测骶骨脊索瘤中的SPHK1与MAPK通路的相关性。方法:我们通过免疫组化检测42例脊索瘤标本和16例瘤旁正常组织标本中SPHK1、RAF-1和ERK1/2的表达,并且进一步分析了SPHK1与RAF-1、ERK1/2的相关性,以及RAF-1和ERK1/2与骶骨脊索瘤临床因素的关系。结果:RAF-1和ERK1/2在骶骨脊索瘤中的表达明显高于瘤旁正常组织(P=0.008,P=0.019)。Spearman相关分析显示SPHK1的过表达与RAF-1和ERK1/2表达呈正相关(P=0.016,P=0.011),并且RAF-1和ERK1/2表达显著相关(P=0.001)。卡方检验和t检验显示,RAF-1的过表达与周围肌肉侵袭(P=0.032)和肿瘤的复发(P=0.002)明显相关,与性别、年龄、肿瘤的大小和部位无关(P0.05)。ERK1/2与肿瘤的大小相关(P=0.044),与性别、年龄、肿瘤的生长部位和复发无关。Kaplan-Meier生存分析显示RAF-1与肿瘤的持续无瘤生存期相关(P0.005),而ERK1/2则与预后无关(P=0.961)。结论:RAF-1和ERK1/2在骶骨脊索瘤中呈高表达,二者与SPHK1表达密切相关,SPHK1可能通过调节MAPK通路来促进脊索瘤侵袭、复发。
[Abstract]:The expression of SPHK1 in sacral chordoma and its correlation with prognosis objective: sacral chordoma is a primary malignant bone tumor prone to local recurrence. Surgical resection is still the first choice of treatment. However, even if the tumor is removed completely, the recurrence rate is still high. So far, researchers have put more effort into studying biomarkers and therapeutic targets. But the molecular mechanism of tumor behavior is still unclear. The purpose of this study is to study the expression of SPHK1 in sacral chordoma and its clinical significance, and to provide a reference for prognosis judgment and molecular targeted therapy of chordoma. We determined the expression of sphingosine kinase 1 (SPHK1) in 42 cases of sacral chordoma and 16 cases of adjacent normal tissue by immunohistochemical staining and real-time quantitative RT-PCR. We also analyzed the relationship between SPHK1 and clinical factors and disease. Results: in 42 cases of sacral chordoma, 29% of 42 cases of sacral chordoma showed high expression of SPHK1. And in the normal tissue next to the tumor, At the same time, the results of Q RT-PCR also showed that the level of SPHK1 m RNA in sacral chordoma was significantly higher than that in the adjacent normal tissue (P 0.05). Chi-square test showed that the high expression of SPHK1 was related to the recurrence of tumor and the invasion of surrounding muscles. Survival analysis showed that the survival time of patients with high expression of SPHK1 was shorter than that of patients with low expression of SPHK1. Conclusion: both m RNA and protein of SPHK1 are overexpressed in chordoma. Associated with the invasion and recurrence of sacral chordoma, The expression of SPHK1 in sacral chordoma and its correlation with MAPK pathway objective: chordoma is a rare form of embryonic residual chordoma. Malignant bone neoplasms. Studies have shown that SPHK1 can regulate the MAPK pathway to promote the occurrence and development of tumor. It is reported that the MAPK pathway is involved in the occurrence and progression of malignant tumors. In this study, the correlation between SPHK1 and MAPK pathway in sacral chordoma was studied. Methods: we detected the expression of SPHK1raf-1 and ERK1/2 in 42 chordoma specimens and 16 adjacent normal tissues by immunohistochemistry. Furthermore, the correlation between SPHK1 and RAF-1ERK1 / 2 was analyzed. Results the expression of RAF-1 and ERK1/2 in sacral chordoma was significantly higher than that in the adjacent normal tissue of sacral chordoma. Spearman correlation analysis showed that the overexpression of SPHK1 was positively correlated with the expression of RAF-1 and ERK1/2, and the expression of RAF-1 was positively correlated with the expression of RAF-1 and ERK1/2. The overexpression of TRAF-1 was significantly correlated with the expression of ERK1/2. The overexpression of RAF-1 was significantly correlated with the invasion of peripheral muscles (P0. 032) and the recurrence of tumor (P0. 002). There was no correlation between sex, age, size and location of tumor. ERK1 / 2 was related to size of tumor, P0.044% to sex, age, age. Kaplan-Meier survival analysis showed that RAF-1 was associated with tumor survival (P 0.005), while ERK1/2 was not associated with prognosis. Conclusion the expression of RAF-1 and ERK1/2 in sacral chordoma is high. SPHK1 may promote the invasion and recurrence of chordoma by regulating the MAPK pathway.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R738.1

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