本文關(guān)鍵詞： POSTN 軟骨肉瘤 免疫組化 預(yù)后　出處：《山東大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：[背景目的]軟骨肉瘤是第三種最常見的原發(fā)于骨的惡性腫瘤(位于多發(fā)性骨髓瘤及骨肉瘤之后),占所有原發(fā)惡性骨腫瘤的20-27%。男女發(fā)病率基本相同,平均診斷年齡在30-60歲之間。一般認(rèn)為,由于存在腫瘤細(xì)胞產(chǎn)生的細(xì)胞外基質(zhì)、分裂細(xì)胞百分率較低以及血管分布不良等因素,導(dǎo)致腫瘤細(xì)胞對放、化療不敏感。因此最有效的治療方法就是廣泛的切除,導(dǎo)致較高的致殘率及較低的生存效率。雖然大多數(shù)軟骨肉瘤生長緩慢并且很少發(fā)生轉(zhuǎn)移,但是它有約24%左右的高復(fù)發(fā)率,術(shù)后復(fù)發(fā)需要更大范圍手術(shù)切除且預(yù)后很差。所以尋找新的靶點對于軟骨肉瘤的治療至關(guān)重要。Periostin(POSTN)為骨膜蛋白,又叫成骨細(xì)胞特異性因子-2,是一種細(xì)胞外基質(zhì)分泌性糖蛋白,由位于人13號染色體上的POSTN基因編碼。POSTN蛋白表達(dá)在很多正常器官或者組織中,對骨、牙齒和心臟瓣膜形成和結(jié)構(gòu)維持起重要作用;同時POSTN在生理性上皮-間葉轉(zhuǎn)化(EMT)及胚胎的正常發(fā)育過程中也起著重要作用。近年來越來越多研究表明,POSTN參與各種腫瘤的發(fā)生發(fā)展過程,如結(jié)直腸癌、頭頸部癌、胰腺癌、卵巢癌、乳腺癌、前列腺癌、胃癌、骨肉瘤和神經(jīng)母細(xì)胞瘤等,促進(jìn)腫瘤的存活、增殖、轉(zhuǎn)移和上皮間葉轉(zhuǎn)化。然而POSTN在軟骨肉瘤中表達(dá)及預(yù)后的研究卻不清楚。本論文主要分析POSTN蛋白在軟骨瘤及軟骨肉瘤中的表達(dá)情況,進(jìn)一步探討在軟骨肉瘤中POSTN蛋白的表達(dá)與臨床各病理參數(shù)及預(yù)后的相關(guān)性。[研究方法]將107例軟骨肉瘤及59例軟骨瘤患者石蠟組織塊制作成組織微陣列,通過免疫組織化學(xué)的方法半定量測定POSTN、Ki67、c-Myc及P53在軟骨肉瘤及軟骨瘤標(biāo)本中的表達(dá)。利用Kaplan-Meier生存分析法探究軟骨肉瘤患者中POSTN表達(dá)水平與總體生存率及無病生存率的相關(guān)性,并建立COX比例回歸風(fēng)險模型分析POSTN作為風(fēng)險因子的評估價值。[結(jié)果分析]POSTN在軟骨肉瘤中的表達(dá)明顯高于其在軟骨瘤中的表達(dá)(X2=15.433,P0.001);低級別軟骨肉瘤中POSTN的表達(dá)也顯著高于軟骨瘤(X2=3.900,P=0.048)。且 POSTN 的表達(dá)與組織學(xué)級別(X2=11.660,P=0.003)、復(fù)發(fā)(X2=8.172,P=0.004)呈明顯正相關(guān),尤其POSTN在低級別級別軟骨肉瘤(I級)與中、高級別軟骨肉瘤(Ⅱ、Ⅲ級)的表達(dá)中具有顯著差異。另外,POSTN 過表達(dá)與 c-Myc(r=0.482,P0.001)、Ki67(r=0.277,P=0.004)及P53(r=0.606,P=0.002)的高表達(dá)顯著相關(guān)。KM生存曲線分析顯示POSTN過表達(dá)會導(dǎo)致患者總體生存率(P=0.003)及無病生存率(P=0.001)的顯著降低。COX多因素分析證實POSTN是影響軟骨肉瘤患者總體生存率(HR:3.016,95%CI:1.009-9.016,P=0.048)及無病生存率(HR:3.305,95%CI:1.086-10.056,P=0.035)的獨立預(yù)后因子。[實驗結(jié)論]與軟骨瘤相比,POSTN蛋白在軟骨肉瘤中的表達(dá)水平顯著增高,且在軟骨肉瘤中POSTN過表達(dá)患者的總體生存率及無病生存率明顯降低,因此POSTN可以作為軟骨肉瘤患者預(yù)后的評價因子。
[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，

本文編號：1504795