Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma
Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma
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DOI：
10.1002/ijc.24297
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发表时间：
2009-06-15
影响因子：
6.4
通讯作者：
Takagi, Ritsuo
中科院分区：
文献类型：
--
作者：
Hirano, Chizuru;Nagata, Masaki;Takagi, Ritsuo
准确评估口腔鳞状细胞癌的恶性程度对优化治疗方案至关重要。为了检测牙龈鳞状细胞癌（GSCC）恶性倾向相关的生物标志物，对四跨膜蛋白家族基因进行定量基因表达分析。对73例GSCC组织提取总RNA，采用真实的时间PCR方法检测基因表达。检测了6个四跨膜蛋白家族基因（CD9、CD63、CD81、CD82、CD151、NAG-2）。管家基因（ACTB和GAPDH）、锚蛋白基因（JUP和PXN）和整联蛋白基因（ITGA 3）用作参考基因。从这些IT基因表达水平计算45个基因表达比率，并使用多变量统计方法与临床参数进行分析。根据以颈淋巴结转移为目标变量的逻辑回归分析的结果，除了肿瘤大小（p = 0.028）之外，CD9/ACTB（p = 0.013）或CD9/CD82（p = 0.013）被检测为显著因素。在考克斯比例风险回归分析中，除了CD 151/GAPDH（p = 0.024）外，迟发颈淋巴结转移（p = 0.039）和肿瘤细胞阳性手术切缘（p = 0.032）也被检测为死亡结局的重要因素。Kaplan-Meier生存曲线显示CD 151/GAPDH值为10或更高的组的生存率显著更低（对数秩和广义Wilcoxon检验：p = 0.0003）。本研究的结果表明，CD9和CD151表达水平作为评估GSCC恶性程度的生物标志物是有用的。他们还指出，在手术切缘残留的肿瘤细胞和肿瘤的生物学恶性程度的检测相互依赖地影响预后。(C)2009年UICC
Accurate assessment of malignancy in oral squamous cell carcinoma is essential to optimize treatment planning. To detect a biomarker related to malignant propensity in gingival squamous cell carcinoma (GSCC), quantitative gene expression analysis of tetraspanin family genes was conducted. In 73 cases of GSCC, total RNA was extracted from carcinoma tissues, and gene expression was analyzed by quantitative real time-PCR. Six tetraspanin family genes (CD9, CD63, CD81, CD82, CD151, NAG-2) were investigated. Housekeeping genes (ACTB and GAPDH), anchor protein genes (JUP and PXN) and an integrin gene (ITGA3) were used as reference genes. Forty-five gene expression ratios were calculated from these It gene expression levels and were analyzed with clinical parameters using multivariate statistical methods. According to the results of the logistic regression analysis subjecting cervical lymph node metastasis as a target variable, CD9/ACTB (p = 0.0.13) or CD9/CD82 (p = 0.013) in addition to tumor size (p = 0.028) were detected as significant factors. In Cox proportional hazards regression analysis, delayed cervical lymph node metastasis (p = 0.039) and tumor cell positive surgical margin (p = 0.032) in addition to CD151/GAPDH (p = 0.024) were detected as significant factors for death outcome. A Kaplan-Meier survival curve presented a significantly lower survival rate of the group with a CD151/GAPDH value of 10 or more (log rank and generalized Wilcoxon tests: p = 0.0003). Results of this study present the usefulness of CD9 and CD151 expression levels as biomarkers for assessment of malignancy in GSCC. They also indicate that detection of residual tumor cells at the surgical margin and the biological malignancy of a tumor interdependently affects prognosis. (C) 2009 UICC