中文摘要
研究目的：
Hepatoma-derived growth factor (HDGF) 是一種獨特的核內生長因子在癌症的形成與發展有著相當重要的角色。這個研究是要來闡明HDGF在口腔癌上表現與臨床病理學的特徵來做分析跟比較。
材料與方法：
我們回朔性收集95位口腔鱗狀上皮癌病人，利用開刀後的檢體做成組織微陣列的標本，再利用組織免疫化學染色法來看HDGF還有血管內皮生長因子 （vascular endothelial growth factor, VEGF）的表現強弱。我們紀錄HDGF及 VEGF的表現並與臨床病理學的特徵進行統計學上的分析
結果:
不論是在口腔癌細胞的細胞核還是細胞質皆可以看到HDGF的表現。在細胞核中的高度表現的HDGF跟口腔腫瘤大小(T stage, P=0.004) 及組織分化程度(histological grade, P=0.013)都有統計學上的意義。在細胞質中的高度表現的HDGF僅跟腫瘤壞死(tumor necrosis, P=0.002)有關. VEGF跟頸部淋巴轉移有相關性（P=0.0021），同時也跟在核中表現的HDGF有關（P=0.0006）。在單變相分析中, 細胞核高度表現之HDGF及高度表現的VEGF跟疾病相關存活、無轉移存活、無局部復發存活有相關性. 在多變相分析中有進一步看出在細胞核中的高度表現的HDGF在疾病相關存活及無局部復發存活是獨立重要的預後因子（P=0.028; P=0.0285）。同時過度表現的VEGF在疾病相關存活、無轉移存活、無局部復發存活上也是獨立的預後因子（P=0.0183; P=0.0461; P=0.0153）
結論:
在這一研究中可以發現在口腔癌的病人有著較高表現的HDGF及VEGF代表著較具侵襲性的腫瘤表現及較差的預後。

Abstract
PURPOSE: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and plays an important role in the development and progression of cancer. The current study aimed to elucidate the correlation between HDGF expression, clinic-pathologic parameters, and associated molecular factors of oral cancer.
MATERIALS AND METHODS: The surgically resected samples from a total of 95 patients with oral cancer (squamous cell carcinoma) were enrolled to construct the tissues microarray (TMA) in this retrospective study. The HDGF expression in TMA of oral cancer was determined by immunohistochemistry. HDGF and vascular endothelial growth factor (VEGF) immunostaining in tumor samples was scored and the labeling index were correlated with various clinic-pathologic parameters by statistic analysis.
RESULTS: Expression of nuclear HDGF and VEGF was highly correlated with primary T stage (P=0.004 and P=0.038, respectively) and histological grade (P=0.013 and P=0.017, respectively). VEGF expression also associated with nodal status (P=0.021). Moreover, expression of nuclear HDGF and VEGF were highly correlated to each other (P=0.006). On the other hand, expression of HDGF in cytoplasm only associated with tumor necrosis (P=0.002) and showed no impact on survival. In univariate analysis, high expression of nuclear HDGF and VEGF significantly affected disease-specific, metastasis-free, and local recurrence-free survival. Multivariate analysis also indicated that expression level of nuclear HDGF is an independent prognostic factor for disease-specific and local recurrence-free survival (P=0.028; P=0.0285). Indeed, high expression of VEGF is also an independent factor in disease-specific, local recurrence-free, and metastasis free survival (P=0.0183; P=0.0461; P=0.0153).
CONCLUSION: The data showed that high expression of nuclear HDGF and VEGF in squamous cell carcinoma of oral cavity might identify patients at risk of aggressive disease and predict poor prognosis. HDGF might play as key of regulation of tumorigenesis. Therefore, HDGF could be a candidate gene for the development of diagnostic and therapeutic strategies for oral cancer. Further studies are still need to determine the precise role of HDGF in the biological behavior of oral caner and the regulatory mechanism with other associated molecular factors.

Abstract 1
English abstract 1
Chinese abstract 3
Introduction 4
Materials and Methods 7
Study population 7
Treatment and follow-up 7
Histopathological examination 9
Construction of tissue microarray (TMA) block 9
Immunohistochemistry (IHC) 10
Immunohistochemical Assessment 11
Statistical analysis 11
Results 13
Characteristics of the oral cancer patients 13
The expression of HDGF and VEGF in oral cancer cell 13
Correlation analysis of HDGF/VEGF and clinicopathological parameter 14
Univariate log-rank analyses of survival---high expression of HDGF and VEGF 15
Multivariate analyses of survival---high expression of HDGF and VEGF 15
Discussion 17
Survival of oral cancer 17
The transporting pathway of HDGF 18
The role of HDGF and VEGF in oral cancer 20
Angiogenesis---the interaction of HDGF and VEGF 23
Conclusion 25
Tables 26
Figures 31
References 40

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