Molecular Profiling and the Identification of Genes Associated With Metastatic Oral Cavity/Pharynx Squamous Cell Carcinoma

Abstract

Objective: 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.Design: 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.Subjects: A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy.Results: Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change Ն1.5; PϽ.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change Ն1.5; PϽ.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11 ␣-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). Conclusions: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.

SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma

“…There are several gene-expression studies that have identified SERPINE1 as an important gene associated with metastasis and this has been supported by IHC analysis in OSCC, but those studies did not use a combined approach on the same tumours (Yasuda et al, 1997;Schmalbach et al, 2004;Roepman et al, 2005;Liu et al, 2008;Mendez et al, 2009). To corroborate and extend our RNA expression analyses, we used IHC to determine differences in expression at the tumour centre and the tumour-advancing front, and to determine which site has the greatest discrimination in relation to pathological variables (Chuaqui et al, 2002).…”

Oral squamous cell carcinoma: Review of prognostic and predictive factors

“…Global RNA expression analysis can be achieved by DNA microarray technology, which has been used in various cancers, 102 including oral cancer, 103,104 to obtain gene expression profiles, associating them subsequently with clinical features. The potential of this method is vast, but one must not forget that cDNA microarray assays can only analyze the transcriptome, whereas biologic function is mediated mostly by proteins.…”

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

“…HNSCC may be a useful system for studying lymphatic metastasis because of the high probability of lymphatic spread and low probability of hematogenous spread. A recent study has identified a gene signature for recurrent disease in HNSCC and several studies have investigated the changes in gene expression from normal tissue to carcinoma, but studies involving lymphatic metastasis have been limited by the small number of genes assessed and/or lack of a rigorous efficacy test of the metastatic signature (Alevizos et al, 2001;Belbin et al, 2002;Mendez et al, 2002;Hwang et al, 2003;Gonzalez et al, 2003;Leethanakul et al, 2003;Nagata et al, 2003;Chung et al, 2004;Ginos et al, 2004;Schmalbach et al, 2004;Warner et al, 2004).…”