BACKGROUND AND AIMS: Genetic alteration associated with initiation and progression of laryngeal squamous cell carcinoma (LSCC) is largely unknown. The aim of this study was to identify genetic changes associated with the disease pathogenesis and pinpoint genes whose expression is impacted by these genetic alterations. METHODS: Tumor cells were collected from eight matched pairs of specimens of glottic carcinoma of the larynx and histologically normal epithelium tissues adjacent to the carcinoma by laser capture microdissection (LCM). RNAs prepared from these cells were used for genome-wide transcriptome analysis by probing 16 cDNA microarrays. Real-time quantitative RT-PCR and immunohistochemistry of tissue microarrays were used to validate a group of the differentially expressed genes identified by the cDNA microarrays. RESULTS: Hierarchical cluster analysis of the expressed genes showed that 2351 genes were differentially expressed and could distinguish cancerous and noncancerous samples. We also found 761 differentially expressed genes that were consistently different between early stage and later stage specimens. Furthermore, abnormal expression of some relevant genes such as MMP12, HMGA2, and TIMP4 were validated by real-time quantitative RT-PCR and immunohistochemistry. Analysis of gene ontology and pathway distributions then highlighted genes that may be critically important to laryngeal carcinogenesis. CONCLUSIONS: Our results suggest that using LCM plus DNA microarray analysis may facilitate the identification of clinical molecular markers for disease and novel potential therapeutic targets for LSCC.
BACKGROUND AND AIMS: Genetic alteration associated with initiation and progression of laryngeal squamous cell carcinoma (LSCC) is largely unknown. The aim of this study was to identify genetic changes associated with the disease pathogenesis and pinpoint genes whose expression is impacted by these genetic alterations. METHODS: Tumor cells were collected from eight matched pairs of specimens of glottic carcinoma of the larynx and histologically normal epithelium tissues adjacent to the carcinoma by laser capture microdissection (LCM). RNAs prepared from these cells were used for genome-wide transcriptome analysis by probing 16 cDNA microarrays. Real-time quantitative RT-PCR and immunohistochemistry of tissue microarrays were used to validate a group of the differentially expressed genes identified by the cDNA microarrays. RESULTS: Hierarchical cluster analysis of the expressed genes showed that 2351 genes were differentially expressed and could distinguish cancerous and noncancerous samples. We also found 761 differentially expressed genes that were consistently different between early stage and later stage specimens. Furthermore, abnormal expression of some relevant genes such as MMP12, HMGA2, and TIMP4 were validated by real-time quantitative RT-PCR and immunohistochemistry. Analysis of gene ontology and pathway distributions then highlighted genes that may be critically important to laryngeal carcinogenesis. CONCLUSIONS: Our results suggest that using LCM plus DNA microarray analysis may facilitate the identification of clinical molecular markers for disease and novel potential therapeutic targets for LSCC.
Authors: Alejandra Valdivia; Raúl Peralta; Manuel Matute-González; Juan Manuel García Cebada; Ivonne Casasola; Cristina Jiménez-Medrano; Rogelio Aguado-Pérez; Vanessa Villegas; Cesar González-Bonilla; Leticia Manuel-Apolinar; Miguel Ibáñez; Mauricio Salcedo Journal: Int J Clin Exp Pathol Date: 2011-10-12
Authors: E Fountzilas; K Markou; K Vlachtsis; A Nikolaou; P Arapantoni-Dadioti; E Ntoula; G Tassopoulos; M Bobos; P Konstantinopoulos; G Fountzilas; D Spentzos Journal: Ann Oncol Date: 2012-01-04 Impact factor: 32.976
Authors: Antonio Palumbo; Nathalia Meireles Da Costa; Francesco Esposito; Marco De Martino; Daniela D'Angelo; Vanessa Paiva Leite de Sousa; Ivanir Martins; Luiz Eurico Nasciutti; Alfredo Fusco; Luis Felipe Ribeiro Pinto Journal: Oncotarget Date: 2016-05-03