PMID- 19237021 OWN - NLM STAT- MEDLINE DCOM- 20090407 LR - 20231213 IS - 1873-5487 (Electronic) IS - 0188-4409 (Linking) VI - 40 IP - 2 DP - 2009 Feb TI - Differential gene expression profiling of laryngeal squamous cell carcinoma by laser capture microdissection and complementary DNA microarrays. PG - 114-23 LID - 10.1016/j.arcmed.2008.12.005 [doi] AB - 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. FAU - Ma, Li-Juan AU - Ma LJ AD - Department of Otolaryngology Head/Neck Surgery, Hunan Provincial People's Hospital, Changsha, PR China. FAU - Li, Wei AU - Li W FAU - Zhang, Xin AU - Zhang X FAU - Huang, Dong-Hai AU - Huang DH FAU - Zhang, Hua AU - Zhang H FAU - Xiao, Jian-Yun AU - Xiao JY FAU - Tian, Yong-Quan AU - Tian YQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arch Med Res JT - Archives of medical research JID - 9312706 RN - 0 (Biomarkers, Tumor) RN - 0 (HMGA2 Protein) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - EC 3.4.24.65 (MMP12 protein, human) RN - EC 3.4.24.65 (Matrix Metalloproteinase 12) SB - IM MH - Aged MH - Biomarkers, Tumor/*genetics MH - Carcinoma, Squamous Cell/*genetics MH - Down-Regulation/genetics MH - Female MH - *Gene Expression Profiling MH - HMGA2 Protein/metabolism MH - Humans MH - Immunohistochemistry MH - Laryngeal Neoplasms/*genetics MH - Male MH - Matrix Metalloproteinase 12/metabolism MH - Microdissection MH - Middle Aged MH - *Oligonucleotide Array Sequence Analysis MH - Tissue Inhibitor of Metalloproteinases/metabolism MH - Up-Regulation/genetics MH - Tissue Inhibitor of Metalloproteinase-4 EDAT- 2009/02/25 09:00 MHDA- 2009/04/08 09:00 CRDT- 2009/02/25 09:00 PHST- 2008/07/13 00:00 [received] PHST- 2008/12/01 00:00 [accepted] PHST- 2009/02/25 09:00 [entrez] PHST- 2009/02/25 09:00 [pubmed] PHST- 2009/04/08 09:00 [medline] AID - S0188-4409(08)00302-0 [pii] AID - 10.1016/j.arcmed.2008.12.005 [doi] PST - ppublish SO - Arch Med Res. 2009 Feb;40(2):114-23. doi: 10.1016/j.arcmed.2008.12.005.