Schmalbach Cecelia E, Chepeha Douglas B, Giordano Thomas J, Rubin Mark A, Teknos Theodoros N, Bradford Carol R, Wolf Gregory T, Kuick Rork, Misek David E, Trask Douglas K, Hanash Samir
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor 48109-0656, USA.
Arch Otolaryngol Head Neck Surg. 2004 Mar;130(3):295-302. doi: 10.1001/archotol.130.3.295.
To investigate differences in gene expression profiles between oral cavity/oropharynx squamous cell carcinoma (OC/OP SCC) primary tumors that have metastasized to cervical lymph nodes and nonmetastatic OC/OP SCC tumors.
Oligonucleotide microarray analysis of primary tumors was used to produce gene expression profiles. Profile comparisons between metastatic and nonmetastatic tumors were performed using principal component analysis, t test, and fold change differences. A similar comparison between metastatic tumors and noncancer oral mucosa samples was performed to ensure tumor origin.
A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy.
Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change > or =1.5; P<.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change > or =1.5; P<.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11 alpha-1 (COL11A1) demonstrated the greatest differential expression between metastatic and nonmetastatic OC/OP SCC tumors (fold change=7.61; P=.002). Tissue inhibitor of metalloproteinase 1 (TIMP-1) also demonstrated increased expression in metastatic tumors (fold change=3.3; P=.003).
Metastatic OC/OP SCC has a distinct gene expression profile compared with nonmetastatic OC/OP SCC and normal oral mucosa. This metastatic profile includes genes related to the extracellular matrix, adhesion, motility, and protease inhibition. Knowledge gained through tumor gene expression profiling may facilitate early detection of aggressive tumors and targeted therapeutic interventions.
研究已转移至颈部淋巴结的口腔/口咽鳞状细胞癌（OC/OP SCC）原发肿瘤与未转移的OC/OP SCC肿瘤之间基因表达谱的差异。
采用原发性肿瘤的寡核苷酸微阵列分析来生成基因表达谱。使用主成分分析、t检验和倍数变化差异对转移瘤和非转移瘤的基因表达谱进行比较。对转移瘤和非癌口腔黏膜样本进行类似比较以确定肿瘤来源。
20例先前未经治疗的OC/OP SCC患者的前瞻性队列，这些患者在手术切除和淋巴结清扫后进行了病理分期。
在约9600个被分析的基因中，101个基因在转移瘤和非转移瘤之间表现出显著的表达差异（倍数变化≥1.5；P<0.01）。在这个子集中，57个基因在转移瘤和正常黏膜样本之间也表现出显著差异（倍数变化≥1.5；P<0.05）。该基因表达谱包括与细胞外基质、黏附、运动、炎症和蛋白酶抑制相关的基因。11型胶原蛋白α-1（COL11A1）在转移的和未转移的OC/OP SCC肿瘤之间表现出最大的差异表达（倍数变化=7.61；P=0.002）。金属蛋白酶组织抑制剂1（TIMP-1）在转移瘤中也表现出表达增加（倍数变化=3.3；P=0.003）。
与未转移的OC/OP SCC和正常口腔黏膜相比，转移的OC/OP SCC具有独特的基因表达谱。这种转移相关的基因表达谱包括与细胞外基质、黏附、运动和蛋白酶抑制相关的基因。通过肿瘤基因表达谱获得的知识可能有助于侵袭性肿瘤的早期检测和靶向治疗干预。
