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Title: | 黏蛋白型O-聚醣在肝癌中的表現情形 Expression of mucin-type O-glycans in hepatocellular carcinoma |
Authors: | Wei-Jen Wang 王韋人 |
Advisor: | 黃敏銓 |
Keyword: | O-型醣化作用,黏蛋白型O-聚醣,肝癌,Tn抗原, O-glycosylation,mucin-type O-glycan,Tn antigen,HCC, |
Publication Year : | 2013 |
Degree: | 碩士 |
Abstract: | 異常的醣化作用是癌細胞常見的一種特徵。腫瘤相關醣抗原─Tn、sialyl-Tn、T和sialyl-T抗原,是由於不正常的黏蛋白型O-聚醣醣化作用所導致。這些腫瘤相關黏蛋白型O-聚醣的表現通常與許多癌症的惡性程度以及預後有直接的相關性。曾有研究指出在肝癌中有腫瘤相關黏蛋白型O-聚醣的表現;然而,這些醣抗原與肝癌的臨床病理特性以及預後之間的關聯性仍不明確。在本篇研究中,我們利用免疫組織化學染色法檢視Tn、sialyl-Tn、T和sialyl-T抗原的在肝癌組織中的表現情形。結果顯示,有76% (69/91)、 58% (29/50)、 26% (13/50)和26% (13/50)的肝癌組織分別表現Tn、sialyl-Tn、T和sialyl-T抗原。其中,Tn抗原的表現和肝癌的腫瘤的大小和侵犯程度(T stage, p < 0.005)、組織分化程度(histological grade, p = 0.001)、有無血管侵襲(vascular invasion, p = 0.001)以及是否復發(recurrence, p < 0.05)都有統計上的正相關。有較高Tn抗原表現的病人,其五年存活率也較差(p < 0.05)。此外,我們也檢視了負責合成黏蛋白型O-聚醣的酵素的mRNA的表現量,包含有GALNTs、ST6GALNACs、ST3GALs、C1GALT1、COSMC、GCNTs、B3GNT3和B3GNT6等幾個酵素家族。結果顯示,GALNT10、ST6GALNAC2和C1GALT1的mRNA表現量在肝癌中有顯著的上升;相反的,GALNT2、ST3GAL1和B3GNT6的mRNA表現量在肝癌中有顯著的下降。此結果顯示,在肝癌病人中不正常的醣化基因的表現,可能是導致異常黏蛋白型O-聚醣表現的原因之一。總結來說,本研究發現在肝癌病人中有不正常Tn、sialyl-Tn、T和sialyl-T抗原;而其中Tn抗原的表現量與肝癌的惡性程度以及預後有顯著的相關。根據這些結果我們推測,異常黏液型O-聚醣的表現以及與其合成相關的醣類基因,在肝癌的發展中可能扮演著重要的角色。 Altered glycosylation is a common feature of cancer cells. Expressions of Tn, sialyl-Tn, T, and sialyl-T antigens are caused by aberrant mucin-type O-glycosylation. These antigens are tumor-associated carbohydrate antigens, and their expressions are often associated with malignant properties and clinical outcome of many cancers. Although the expressions of these antigens in hepatocellular carcinoma (HCC) have been reported, the correlation between their expressions and clinicapathological features and prognosis is still unclear. In this study, immunohistochemistry showed that the prevalence of Tn, sialyl-Tn, T, and sialyl-T antigens in human HCC tissues was 76% (69/91), 58% (29/50), 26% (13/50), and 26% (13/50), respectively. The expression level of Tn antigens was positively associated with advanced T stage (p < 0.005) and higher histological grade (p = 0.001), as well as increased vascular invasion (p = 0.001) and recurrence (p < 0.05) of HCC. In addition, high expression of Tn antigens significantly correlated with poor 5-year survival of HCC patients (p < 0.05). Furthermore, we analyzed the mRNA expression of glycogenes for O-glycan synthesis, including GALNTs, ST6GALNACs, ST3GALs, C1GALT1, COSMC, GCNTs, B3GNT3, and B3GNT6, in human HCC tissues by real-time RT-PCR. Among them, the mRNA levels of GALNT10, ST6GALNAC2, and C1GALT1 were significantly up-regulated, while GALNT2, ST3GAL1, and B3GNT6 were significantly down-regulated in HCC tissues compared with those in the non-tumor part. These results suggest that the expression of aberrant O-glycans in HCC may be resulted from the dysregulation of these glycogenes. In conclusion, our findings suggest that Tn, sialyl-Tn, T, and sialyl-T antigens are expressed in HCC, and the expression of Tn antigens is associated with poor prognosis of HCC patients. These results imply that mucin-type O-glycans and O-glycogenes may play roles in modulating tumor progression of HCC. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62562 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 解剖學暨細胞生物學科所 |
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