基質細胞衍生因子-1 (SDF-1)及其受體CXCR4之基因多型性與肝細胞癌的相關性探討

Study of the stromal cell-derived factor-1(SDF-1) and CXCR4 gene polymorphism in hepatocellular carcinoma

張啟中(Chi-Chung Chang)

指導教授 ： 周明智

中山醫學大學/醫學院/醫學研究所/博士(2009年)

https://doi.org/10.6834/CSMU.2009.00053

摘要

研究目的：肝細胞癌 (hepatocellular carcinoma; HCC)目前是全世界常見的惡性腫瘤之一。在台灣地區，每年也是在癌症死亡率的第二名。而有諸多研究報告曾指出，單核苷酸基因多型性(Single Nucleotide Polymorphism; SNP) 被認為與罹患惡性腫瘤的風險有關，也可以當作一個預測因子。而之前有文獻曾指出，在肝細胞癌腫瘤細胞增殖、血管新生與腫瘤細胞轉移上，基質細胞衍生因子-1 (stromal cell-derived factor-1; SDF-1)與它的受體CXCR4（CXC chemokine Receptor 4），扮演著重要的角色。因此，本研究之目的，即在於評估在SDF-1與CXCR4的基因多型性與罹患肝細胞癌的風險及其與臨床病理狀態為何。

研究方法及資料：本研究利用聚合酶連鎖反應限制片段長度多型性分析（PCR-RFLP）的方式，針對三百一十一位的健康對照組與一百零二位的肝細胞癌患者，進行這些受測者的SDF-1 (rs1801157) 與 CXCR4 (rs2228014) 之基因多型性分析。

研究結果：經與健康對照組的受試者比對後發現，肝細胞癌患者若至少具有一個A等位基因，經由校正不同比對因子後，則至少有1.57倍的高風險 (95% CI: 1.00-2.47)會誘發成肝細胞癌，同時有2.81倍的高風險 (95% CI: 1.04-7.58) 誘發成肝細胞癌第三期或第四期。然而，CXCR4的基因多型性與罹患肝細胞癌風險或不同的病理狀態中都沒有明顯的相關性。此外，本研究進一步比對肝細胞癌患者其SDF-1與CXCR4之基因多型性與肝細胞癌患者相關之臨床病理指標的血清濃度的相關性，結果發現其中並無明顯的關聯性。因此，本研究發現SDF-1-的基因多型性，可被視為促進肝細胞癌的發生與其病理上發展成肝細胞癌之相關因子。

結論與建議：以本研究的結果，推論罹患肝細胞癌患者中，諸多造成肝細胞癌的因子中，與SDF-1的基因多型性有關，而與其受體CXCR4基因多型性無關，因此，希望可以將SDF-1的基因多型性應用到肝細胞癌研究中，並期許可以當作一個促進或發展成肝細胞癌病理上的可能因子。

關鍵字

基質細胞衍生因子－1 ； 單核苷酸基因多型性 ； 肝細胞癌

並列摘要

Objective：Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms in the world. Death rate of HCC is the second rank of all cancer population in Taiwan, Genetic polymorphism has been reported as a factor to increase the risk of HCC. In the previously studies, stromal cell-derived factor-1 (SDF-1) and its receptor, a CXC chemokine Receptor 4（CXCR4）, play important roles in tumor cell proliferation, angiogenesis, and metastasis. The aim of this study was to estimate the relations of SDF-1 and CXCR4 gene variants on HCC risk and clinicopathological status.

Methods and Materials：Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to measure SDF-1 (rs1801157) and CXCR4 (rs2228014) gene polymorphisms in 311 healthy controls and 102 patients with HCC.

Results：The individuals with at least one mutated A allele had 1.57 fold risk (95% CI: 1.00-2.47) to induce HCC and had 2.81 fold risk (95% CI: 1.04-7.58) to develop stage III or stage IV, after adjustment for other confounders. However, there was no significantly association between CXCR4 gene polymorphism and either HCC risk or pathological status. Additionally, both gene polymorphisms were not associated with the serum expression of liver-related clinical pathological markers.

Conclution and suggestion： In conclusion, SDF-1-3’A gene polymorphism could be considered as a factor increasing the susceptibility and pathological development of HCC.

並列關鍵字

Stromal cell-derived factor-1 (SDF-1) ； CXC chemokine Receptor 4（CXCR4） ； Hepatocellular carcinoma (HCC) ； Single Nucleotide Polymorphism ； (SNP)

參考文獻

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