SOX-9於口腔鱗狀細胞癌之表現

The Expression of SOX-9 in Oral Squamous Cell Carcinomas

楊方瑜(Fang-Yu Yang)

指導教授 ： 郭彥彬 ； 江俊斌

國立臺灣大學/牙醫專業學院/臨床牙醫學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.01402

摘要

背景: SOX-9在許多組織分化中扮演重要角色，例如軟骨生成、胚胎性別分化、呼吸上皮發育、黑素細胞分化、腸道中的潘氏細胞(Paneth cell)的分化等，都與SOX-9有關。同時SOX-9在癌症中的影響亦逐漸被發掘，例如大腸直腸癌、攝護腺癌、卵巢癌等。許多研究顯示SOX-9對於腫瘤的生長及轉移呈現正相關，且SOX-9的過度表現會有較差的預後；然而亦有研究顯示SOX-9扮演了抑癌功能，故其在癌症中所扮演的角色尚須被釐清。目前尚未有針對SOX-9與口腔癌相關之研究報告，因此本實驗針對SOX-9在口腔癌的表現做一研究分析。
材料與方法: 本研究利用免疫組織化學染色方法，探討SOX-9於100例口腔鱗狀細胞癌(OSCC)、61例口腔上皮變異(OED)及40例正常口腔黏膜(NOM)中的表現。利用 ANOVA、卡方檢定(Chi-square test)、Kaplan-Meier 存活率方法及Cox proportional hazard regression model來分析SOX-9的表現與口腔鱗狀細胞癌患者臨床病理參數及存活率之相關性，並試圖尋找影響存活時間的獨立預後因子。
結果: SOX-9在正常口腔黏膜的平均陽性標記指數為4% (最低)，口腔上皮變異組的平均陽性標記指數分別為9%(輕度上皮變異)、18%(中度上皮變異)、29%(重度上皮變異)，口腔癌組的平均陽性標記指數為 48% (最高)，可以看出從正常口腔黏膜、上皮變異至口腔癌，這個癌化的過程中，SOX-9的表現增加的情形，且有達統計意義(P < 0.001)。SOX-9的表現和患者的腫瘤大小、淋巴結轉移與否、癌症臨床分期有統計上相關。
單變數分析當中，腫瘤大小(T)、淋巴結轉移情形(N)、腫瘤分期(S)、SOX-9陽性標記指數(LI)都跟存活時間有關 ( p <0.05)；經過 Cox regression model 進行多變數分析以後, 僅有淋巴結轉移情形(N)、腫瘤分期(S)、SOX-9 LI為影響存活時間的獨立因子 ( p <0.05 )。
結論: 在本研究中，SOX-9在腫瘤中表現較高且具統計上意義；此外，SOX-9的表現與口腔鱗狀細胞癌患者相關的臨床參數及存活率有相關。

關鍵字

SOX-9 ； 口腔鱗狀細胞癌 ； 口腔上皮變異

並列摘要

Background:
SOX-9 plays an important role in many tissue differentiation processes, eg. chondrogenesis, male sex gonad differentiation, respiratory epithelim development, melanocyte differentiation, and the differentiation of the Paneth cells in guts. Also, numerous cancer studies focused on the influences of SOX-9, on colorectal cancer, prostate cancer, and ovarian cancer. Lots of the studies showed that the up-regulation of SOX-9 was correlated to the tumor growth and tumor cell metastasis, and the overexpression of SOX-9 indicated a poor prognosis. However, other studies pointed out that SOX-9 may act as a tumor repressor. So the role of SOX-9 in cancers was still equivocal. Until now, the relationship between SOX-9 and oral squamous cell carcinoma is unclear. Therefore, this study tried to elucidate the expression pattern of SOX-9 in OSCC and to correlate the expression of SOX-9 to the clinicopathological findings and long-term prognosis.
Material and Method:
In this study, we examined the expression of SOX-9 in 100 specimens of oral squamous cell carcinoma (OSCC), 61 specimens of oral epithelial dysplasia (OED), and 40 specimens of normal oral mucosa (NOM) by immunohistochemistry. The correlation between the expression of SOX-9 in OSCCs and clinicopathological parameters or the survival of OSCC patients was analyzed by ANOVA, Chi-square and Kaplan-Meier survival analysis. Univariate and multivariate analyses (Cox proportional hazard regression model) were used to find the correlation between expression of SOX-9 and clinicopathological parameters or survival, and tried to find out the independent predictors for the patients’ survival.
Results:
The labeling indices of SOX-9 significantly increased from NOM (4%, the lowest), through mild dysplasia (9%), moderate dysplasia (18%), and severe dysplasia (29%) to OSCC (48%) (p<0.001). The expression of SOX-9 was correlated with tumor size, lymph node status and clinical stage (p<0.05). Univariate analysis showed that tumor size, lymph node status, clinical stage and SOX-9 LI are related to the survival time (p<0.05). Multivariate analysis demonstrated that lymph node metastasis, clinical stage and SOX-9 LI were independent predictors for the patients’ survival (p<0.05).
Conclusion:
In this study, the expression of SOX-9 was significantly higher in OSCC than that in NOM and OED. In addition, SOX-9 was correlated with several clinical parameters and patients’ survival. SOX-9 may be a prognostic factor for OSCC patients.

並列關鍵字

SOX-9 ； oral squamous cell carcinoma ； oral epithelial dysplasia

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