Gene expression changes in initiation and progression of oral squamous cell carcinomas revealed by laser microdissection and oligonucleotide microarray analysis

Background. Oral carcinogenesis is a complex process involving multiple genes. However, the genetic changes involved in this process are not demonstrated in the identical oral squamous carcinomas (OSCCs). Methods. According to the pathological characteristics, parts of normal tissues, oral dysplastic lesions (ODLs), and invasive cancers were procured from the identical OSCCs using laser microdissection (LMD), and large scale gene expression profiling was carried out on 33 samples derived from 11 OSCCs. Results. We analyzed genes differentially expressed in normal tissues vs. ODLs and ODLs vs. invasive tumors and identified the 15 candidate genes that continuously increasing or decreasing in its expression during oral carcinogenesis. One of these, ISG15 was chosen for further characterization. Real-time quantitative reverse transcriptase-polymerase chain reaction and immunohistochmistry analysis confirmed that ISG15 expression was consistently increasing during oral tumorigenesis. ISG15 high expression was significantly associated with poor prognosis (P=0.027). In addition, patients whose tumor had high ISG15 expression had worse 5-year survival rate than patients whose tumors had a low expression level (P=0.019). Conclusions. We identified the 15 genes that are continuously increasing or decreasing in its 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 in these malignancies. Microarray samples of invasive tumor, adjacent dysplastic lesions and noncancerous normal tissues were collected from 11 patients with primary OSCCs. We analyzed genes differentially expressed in (i) normal vs. dysplastic tissues and (ii) dysplastic vs. tumor tissues.