基質細胞衍生因子(SDF-1)受體CXCR4在口腔鱗狀細胞癌的表現與癌症進展風險

The stromal cell-derived factor-1(SDF-1) receptor, CXCR4 expression in oral squamous cell carcinoma and risk of tumor progression

蘇金泉(Chin-Chuan Su)

指導教授 ： 張文正

長榮大學/健康科學學院/醫學研究所/碩士(2012年)

https://doi.org/10.6833/CJCU.2012.00099

摘要

研究目的：口腔部位是頭頸部鱗狀細胞癌（head and neck squamous cell carcinoma, HNSCC）最常見的位置之一。在台灣，口腔癌是男性十大癌症死因的第四位。在過去十年，口腔癌在臺灣的發生率與死亡率大幅上升，是近十年來所有癌症發生率與死亡率增加幅度最多的癌症。近年來，化學激素(chemokines)被發現是腫瘤形成和轉移的一個重要發展因子。之前研究指出現基質細胞衍生因子-1(stromal cell-derived factor-1)及其受體CXCR4 (CXC chemokine receptor 4)在許多癌症形成過程中與腫瘤增生、血管新生、局部淋巴轉移和遠處器官轉移等過程有關。因此，本研究的目的是藉由組織顯微晶片(tissue microarray)方式來研究CXCR4在口腔鱗狀細胞癌的表現與臨床病理因子、生存預後的相關性。
方法：收集從1999年8月至2007年12月在彰化基督教醫院主要以接受手術方式治療的口腔鱗狀細胞癌患者。藉由組織微陣列(TMA)使用免疫組織化學染色方式，分析289位口腔鱗狀細胞癌患者CXCR4在口腔原發腫瘤的表現與其臨床病理表現因子如腫瘤大小、淋巴結轉移、遠處器官轉移和患者存活率之間的關聯。
結果：總共有289位口腔癌患者並接受手術治療進行此一回溯性研究。患者年齡從31歲至80歲，平均年齡為 55.5歲。結果發現在289例口腔癌原發腫瘤中有80例(27.7%)表現CXCR4。分析CXCR4在口腔鱗狀細胞癌(OSCC)的表現與各項臨床病理因子的關係發現，CXCR4表現與原發腫瘤大小的發展有關(P=0.005)但與頸部淋巴結轉移、遠處器官轉移和臨床分期無關。利用Kaplan-Meier plots存活率分析本研究289位口腔鱗狀細胞癌患者存活曲線結果發現CXCR4在口腔原發腫瘤表現與存活率亦無相關。
結論：我們發現患口腔癌病患在口腔原發腫瘤表現陽性及陰性的CXCR4比較之下， CXCR4陽性染色表現在原發腫瘤大小的發展有較高的風險(P=0.005)。在本篇論文的研究結果中發現CXCR4在口腔癌腫瘤的表現與原發腫瘤大小發展有關，這項發現證實了之前的臨床前實驗室研究，其有關CXCR-4及其配體 (SDF-1)可以調控腫瘤細胞增生及侵襲的能力的觀察。

關鍵字

口腔鱗狀細胞癌 ； CXCR4 ； 組織組織微陣列

並列摘要

Back ground: The oral cavity is one of the most common locations of squamous cell carcinoma in head and neck region. Oral cancer is ranked as the fourth leading cause of cancer death among males. Over the last decade, a significant rise in incidence and mortality of oral cancer has been noted in Taiwan, and in oral cancer there is largest increase in incidence rate and mortality rate among all cancers . In recent years, chemokines are found to be an important factor associated with tumor formation and metastasis. Moreover, it is recently reported that SDF-1 and its receptor CXCR4 are involved in tumor proliferation, neoangiogenesis, lymph node metastasis and distant dissemination.
The purposes of this study were to investigate CXC chemokine receptor 4 (CXCR4) expression on oral squamous cell carcinoma and elucidate the association of CXCR4 receptor expression with clinicopathological factor and with the prognosis of survival of oral squamous cell carcinoma.
Methods: From August 1999 to December 2007, patients with oral cancer treated with primary surgical approach in Changhua Christian Hospital were enrolled in this study. CXCR4 expression was evaluated by immunohistochemical staining using a tissue microarray (TMA) containing samples from 298 oral tumors. The association between CXCR4 expression and several clinicopathological factor, including tumor size, lymph node metastasis, distant metastasis, and survival were assessed.
Results: A total of 289 consecutive patients (operated between August, 1999 and December 2007) with a median age of 55.5 (range 31 to 80) years were retrospectively evaluated. CXCR4 was expressed in 27.7% of oral primary tumor (80 of 289). The association between CXCR4 expression and several clinicopathological factors were evaluated. The expression of CXCR4 was associated with tumor size (P = 0.05), but not lymph node metastasis, distant metastasis or clinical stage. Cumulative survival was analyzed with the Kaplan–Meier method. There was also no statistical significance between CXCR4 and cumulative survival.
Conclusion: Our study demonstrates that the CXCR4 receptor is expressed in 27.7% of oral tumor samples, and that this expression is associated with tumor progression (P=0.005). This finding confirms observations from previous preclinical studies that CXCR4 and its ligand, SDF-1 can modulate tumor cell proliferation and invasiveness.

並列關鍵字

Oral squamous cell carcinoma (OSCC) ； CXCR4 ； Tissue microarray

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