Expression of hypoxia-inducible factor-1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan
Expression of hypoxia-inducible factor-1α is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan
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DOI：
10.1111/j.1600-0714.2007.0057.x
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Chiang, Chun-Pin
中科院分区：
文献类型：
--
作者：
Lin, Pin-Yi;Yu, Chuan-Hang;Chiang, Chun-Pin
背景：低氧抑制因子-1α(HIF-1α)的过度表达与多种人类肿瘤的侵袭、淋巴结转移、临床分期及预后密切相关。方法：检测57例口腔鳞状细胞癌(OSCC)、41例口腔上皮异型增生(OSCD)组织中HIF-1α的表达，其中轻度口腔鳞癌12例，中度口腔鳞癌17例，重度口腔鳞癌12例。结果：口腔鳞癌组织中HIF-1α平均核标记指数(LIS)由正常口腔黏膜(9.6%)、轻度口腔鳞癌(25.18%)、中度口腔鳞癌(41.27%)、重度口腔鳞癌(42.22%)到口腔鳞癌(55.23%，P<；0.001)。HIF-1αLI与肿瘤大小(P<；0.001)、区域淋巴结转移(P<；0.001)或临床分期较晚期(P<；0.00 1)的口腔鳞状细胞癌显著相关。COX回归模型多因素分析显示，只有较大的肿瘤体积(P=0.002)和核HIF-1αLI=60%(P=0.048)是独立的预后不良因素。Kaplan-Meier曲线显示，HIF-1α表达水平为60%的口腔鳞癌患者的累积生存率显著低于HIF-1α水平为60%的口腔鳞癌患者(Log-ranch检验，P=0.022)。结论：口腔鳞癌组织中HIF-1α的表达是口腔癌发生的早期事件。口腔鳞癌组织中核HIF-1αLI的表达可预测口腔鳞癌的进展和患者的生存。
BACKGROUND: Overexpression of hypoxia-inclucible factor-1 alpha (HIF-1 alpha) has been found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, and prognosis of a variety of human cancers.METHODS: This study examined the expression of HIF-1 alpha in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry.RESULTS: We found that the mean nuclear HIF-1 alpha labeling indices (Lis) increased significantly from NOM (9 6%) through mild OED (25 18%), moderate OED (41 27%), and severe OED (42 22%) to OSCC samples (55 23%, P < 0.001). A significant correlation was found between the higher mean nuclear HIF-1 alpha LI and OSCCs with larger tumor size (P < 0.001), regional lymph node metastasis (P < 0.001), or more advanced clinical stages (P < 0.00 1). Only larger tumor size (P = 0.002) and nuclear HIF-1 alpha LI >= 60% (P = 0.048) were identified as independent unfavorable prognosis factor by multivariate analyses with Cox regression model. Kaplan-Meier curve showed that OSCC patients with a nuclear HIF-1 alpha LI >= 60% had a significantly poorer cumulative survival than those with a nuclear HIF-1 alpha LI < 60% (log-rank test, P = 0.022).CONCLUSIONS: We conclude that the expression of HIF-1 alpha is an early event in oral carcinogenesis. The nuclear HIF-1 alpha LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.