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细胞角蛋白17信使核糖核酸表达具有作为口腔鳞状细胞癌诊断标志物的潜力。

Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma.

作者信息

Toyoshima Takeshi, Vairaktaris Eleftherios, Nkenke Emeka, Schlegel Karl Andreas, Neukam Friedrich Wilhelm, Ries Jutta

机构信息

Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Glueckstrasse 11, 91054 Erlangen, Germany.

出版信息

J Cancer Res Clin Oncol. 2008 Apr;134(4):515-21. doi: 10.1007/s00432-007-0308-8. Epub 2007 Sep 4.

Abstract

PURPOSE

Determination of marker for identification of oral squamous cell carcinoma (OSCC) is important for early diagnosis and individual therapy. Cytokeratins (CKs) like CK 19 and CK 20 are known to be useful diagnostic and prognostic markers for solid tumors. The aim of this study was to evaluate the relevance of further CKs for diagnosis of OSCC.

MATERIALS

In 10 OSCC and 5 normal mucosal samples, the expression patterns of 31 CK genes were examined by cDNA microarray in order to identify CKs with most pronounced over-expression. The results were verified for CK 17, CK 19, and CK 20 in addition to 46 OSCC samples by relative quantification (RQ) using SYBR green real-time reverse transcriptase polymerase chain reaction (RT qPCR). A correlation of the CK expressions with the tumor classification was carried out.

RESULTS

cDNA microarray analyses showed that out of all CKs, CK 17 was up-regulated strongest in OSCC compared to normal samples, and over-expression was most significantly associated with diagnosis (P = 0.002). Expression rates of CK 19 and CK 20 were not significantly different between OSCC samples and normal samples. In 56 samples analyzed by real-time RT qPCR, CK 17 was over-expressed in 53 (94.6%), CK 19 in 18 (32.1%), and CK 20 in 7 (12.5%). The over-expression of CK 17 was significantly associated with metastases of neck lymph nodes (P < 0.05). CK 19 was significantly over-expressed in T3 and T4 OSCC, in stage III and IV patients (P < 0.05), and in poorly differentiated OSCC (P < 0.03). The over-expression of CK 20 was significantly associated with metastases of neck lymph nodes (P < 0.03). Determined by RQ, the mean value of CK 17 over-expression was significantly higher than that of the other CKs (P < 0.01), and was significantly associated with T1 and T2 OSCC (P < 0.03) and with stage I and II patients (P < 0.01).

CONCLUSION

CK 19 might be linked to the clinical progression and differentiation of OSCC, and CK 20 could be associated with metastases of neck lymph nodes in OSCC. Due to the significant up-regulation and the strong over-expression, CK 17 might be the most suitable marker for diagnosis of OSCC out of the CK-family.

摘要

目的

确定用于口腔鳞状细胞癌(OSCC)鉴别的标志物对于早期诊断和个体化治疗至关重要。细胞角蛋白(CKs)如CK 19和CK 20已知是实体瘤有用的诊断和预后标志物。本研究的目的是评估其他CKs对OSCC诊断的相关性。

材料

在10例OSCC和5例正常黏膜样本中,通过cDNA微阵列检测31种CK基因的表达模式,以鉴定过表达最明显的CKs。除46例OSCC样本外,还通过使用SYBR Green实时逆转录聚合酶链反应(RT qPCR)的相对定量(RQ)对CK 17、CK 19和CK 20的结果进行了验证。对CK表达与肿瘤分类进行了相关性分析。

结果

cDNA微阵列分析显示,在所有CKs中,与正常样本相比,CK 17在OSCC中上调最强,且过表达与诊断最显著相关(P = 0.002)。OSCC样本和正常样本之间CK 19和CK 20的表达率无显著差异。在通过实时RT qPCR分析的56个样本中,CK 17在53个样本(94.6%)中过表达,CK 19在18个样本(32.1%)中过表达,CK 20在7个样本(12.5%)中过表达。CK 17的过表达与颈部淋巴结转移显著相关(P < 0.05)。CK 19在T3和T4期OSCC、III期和IV期患者(P < 0.05)以及低分化OSCC(P < 0.03)中显著过表达。CK 20的过表达与颈部淋巴结转移显著相关(P < 0.03)。通过RQ测定,CK 17过表达的平均值显著高于其他CKs(P < 0.01),且与T1和T2期OSCC(P < 0.03)以及I期和II期患者(P < 0.01)显著相关。

结论

CK 19可能与OSCC的临床进展和分化有关,CK 20可能与OSCC颈部淋巴结转移有关。由于显著上调和强烈过表达,CK 17可能是CK家族中诊断OSCC最合适的标志物。

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