Periostin在软骨肉瘤患者中的表达特征及预后相关性分析

发布时间：2018-02-12 04:37

  本文关键词： POSTN 软骨肉瘤 免疫组化 预后　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：[背景目的]软骨肉瘤是第三种最常见的原发于骨的恶性肿瘤(位于多发性骨髓瘤及骨肉瘤之后),占所有原发恶性骨肿瘤的20-27%。男女发病率基本相同,平均诊断年龄在30-60岁之间。一般认为,由于存在肿瘤细胞产生的细胞外基质、分裂细胞百分率较低以及血管分布不良等因素,导致肿瘤细胞对放、化疗不敏感。因此最有效的治疗方法就是广泛的切除,导致较高的致残率及较低的生存效率。虽然大多数软骨肉瘤生长缓慢并且很少发生转移,但是它有约24%左右的高复发率,术后复发需要更大范围手术切除且预后很差。所以寻找新的靶点对于软骨肉瘤的治疗至关重要。Periostin(POSTN)为骨膜蛋白,又叫成骨细胞特异性因子-2,是一种细胞外基质分泌性糖蛋白,由位于人13号染色体上的POSTN基因编码。POSTN蛋白表达在很多正常器官或者组织中,对骨、牙齿和心脏瓣膜形成和结构维持起重要作用;同时POSTN在生理性上皮-间叶转化(EMT)及胚胎的正常发育过程中也起着重要作用。近年来越来越多研究表明,POSTN参与各种肿瘤的发生发展过程,如结直肠癌、头颈部癌、胰腺癌、卵巢癌、乳腺癌、前列腺癌、胃癌、骨肉瘤和神经母细胞瘤等,促进肿瘤的存活、增殖、转移和上皮间叶转化。然而POSTN在软骨肉瘤中表达及预后的研究却不清楚。本论文主要分析POSTN蛋白在软骨瘤及软骨肉瘤中的表达情况,进一步探讨在软骨肉瘤中POSTN蛋白的表达与临床各病理参数及预后的相关性。[研究方法]将107例软骨肉瘤及59例软骨瘤患者石蜡组织块制作成组织微阵列,通过免疫组织化学的方法半定量测定POSTN、Ki67、c-Myc及P53在软骨肉瘤及软骨瘤标本中的表达。利用Kaplan-Meier生存分析法探究软骨肉瘤患者中POSTN表达水平与总体生存率及无病生存率的相关性,并建立COX比例回归风险模型分析POSTN作为风险因子的评估价值。[结果分析]POSTN在软骨肉瘤中的表达明显高于其在软骨瘤中的表达(X2=15.433,P0.001);低级别软骨肉瘤中POSTN的表达也显著高于软骨瘤(X2=3.900,P=0.048)。且 POSTN 的表达与组织学级别(X2=11.660,P=0.003)、复发(X2=8.172,P=0.004)呈明显正相关,尤其POSTN在低级别级别软骨肉瘤(I级)与中、高级别软骨肉瘤(Ⅱ、Ⅲ级)的表达中具有显著差异。另外,POSTN 过表达与 c-Myc(r=0.482,P0.001)、Ki67(r=0.277,P=0.004)及P53(r=0.606,P=0.002)的高表达显著相关。KM生存曲线分析显示POSTN过表达会导致患者总体生存率(P=0.003)及无病生存率(P=0.001)的显著降低。COX多因素分析证实POSTN是影响软骨肉瘤患者总体生存率(HR:3.016,95%CI:1.009-9.016,P=0.048)及无病生存率(HR:3.305,95%CI:1.086-10.056,P=0.035)的独立预后因子。[实验结论]与软骨瘤相比,POSTN蛋白在软骨肉瘤中的表达水平显著增高,且在软骨肉瘤中POSTN过表达患者的总体生存率及无病生存率明显降低,因此POSTN可以作为软骨肉瘤患者预后的评价因子。
[Abstract]:[background] chondrosarcoma is the third most common primary malignant tumor of bone (located behind multiple myeloma and osteosarcoma, accounting for 20-27% of all primary malignant bone tumors). The average diagnostic age is between 30 and 60 years old. It is generally believed that the presence of extracellular matrix produced by tumor cells, low percentage of mitotic cells and poor distribution of blood vessels lead to tumor cell exposure. Chemotherapy is insensitive. So the most effective treatment is extensive resection, which leads to higher disability rate and lower survival efficiency. Although most chondrosarcomas grow slowly and rarely metastasize, they have a high recurrence rate of about 24%. Postoperative recurrence requires extensive surgical resection and poor prognosis. Therefore, finding new targets is essential for the treatment of chondrosarcoma. Periostin post post (POSTN) is also called osteoblast specific factor-2, which is an extracellular matrix secretory glycoprotein. The expression of .POSTN protein encoded by POSTN gene located on human chromosome 13 plays an important role in the formation and maintenance of bone, teeth and heart valve in many normal organs or tissues. POSTN also plays an important role in the physiological epithelial-mesenchymal transformation (POSTN) and the normal development of embryos. In recent years, more and more studies have shown that POSTN is involved in the occurrence and development of various tumors, such as colorectal cancer, head and neck cancer, pancreatic cancer. Ovarian cancer, breast cancer, prostate cancer, gastric cancer, osteosarcoma, neuroblastoma, and so on, promoting tumor survival and proliferation, However, the expression and prognosis of POSTN in chondrosarcoma were not clear. This paper mainly analyzed the expression of POSTN protein in chondroma and chondrosarcoma. To further investigate the correlation between the expression of POSTN protein and clinical pathological parameters and prognosis in chondrosarcoma. Immunohistochemical method was used to semi-quantitatively detect the expression of POSTN Ki67 c-Myc and p53 in chondrosarcoma and chondroma. The relationship between POSTN expression and overall survival rate and disease-free survival rate in chondrosarcoma patients was investigated by Kaplan-Meier survival assay. The COX proportional regression risk model was established to analyze the value of POSTN as a risk factor. [results] the expression of POSTN in chondrosarcoma was significantly higher than that in chondroma, and the expression of POSTN in chondrosarcoma was significantly higher than that in chondroma. The expression of POSTN in chondrosarcoma was also significantly higher than that in chondrosarcoma. The expression of POSTN was positively correlated with the histologic grade of X2O11.660P0. 003, and the recurrence of X2 + 8. 172P0. 004 (P < 0. 004), and the expression of POSTN was significantly higher than that of chondroma X2 + 3.900 (P < 0. 048), and the expression of POSTN was positively correlated with the histological grade. In particular, POSTN is present in low grade chondrosarcoma grade I) and in middle and high grade chondrosarcoma (鈪，

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