title: Gene expression changes in initiation and progression of oral squamous cell carcinomas revealed by laser microdissection and oligonucleotide microarray analysis.
abstract: Oral carcinogenesis is a complex process involving multiple genes. However, the genetic changes involved in this process are not apparent in identical oral squamous cell carcinomas (OSCCs). According to pathological characteristics, samples of normal tissue, oral dysplastic lesions (ODLs), and invasive cancers were obtained from identical OSCCs using laser microdissection (LMD). Large-scale gene expression profiling was carried out on 33 samples derived from 11 OSCCs. We analyzed genes differentially expressed in normal tissues vs. ODLs and in ODLs vs. invasive tumors and identified 15 candidate genes with continuously increasing or decreasing expression during oral carcinogenesis. One of these genes, ISG15, was chosen for further characterization. Real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis confirmed that ISG15 expression consistently increased during oral tumorigenesis. An ISG15 high-expression level was significantly associated with poor prognosis (p = 0.027). In addition, patients with high-expression tumors had a poorer 5-year survival rate than patients with low expression levels (p = 0.019). In conclusion, we identified 15 genes with continuously increasing or decreasing expression during oral carcinogenesis. One of these, ISG15, is likely to be associated with both dysgenesis and tumorigenesis and may be a potential prognostic marker for oral cancer.
authors: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Jun
authors: J
authors: Sumino
authors: Narikazu
authors: N
authors: Uzawa
authors: Norihiko
authors: N
authors: Okada
authors: Ken
authors: K
authors: Miyaguchi
authors: Kaoru
authors: K
authors: Mogushi
authors: Ken-Ichiro
authors: K
authors: Takahashi
authors: Hiroaki
authors: H
authors: Sato
authors: Chieko
authors: C
authors: Michikawa
authors: Yoshimi
authors: Y
authors: Nakata
authors: Hiroshi
authors: H
authors: Tanaka
authors: Teruo
authors: T
authors: Amagasa
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D012333:RNA, Messenger; D014452:Ubiquitins; C074034:ISG15 protein, human