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.

HOPX functions as a tumour suppressor in head and neck cancer

“…To examine the potential functional significance of HOPX loss in HNSCCs, we performed gene ontology analysis of genes regulated by HOPX in H376 that were also altered in primary tumours. To do this, we identified genes that were down-regulated by HOPX in H376 but up-regulated in micro-dissected OSCCs and vice versa (GSE35261 dataset16). Gene ontology analyses on these genes identified pathways associated with cell proliferation, adhesion and migration, as well as pathways that regulate epithelial development and differentiation (Fig.…”

“…Rather than validate a limited number of the transcriptional changes in vitro , we adopted an approach to identify pathways that were functionally relevant in tumours. To do this we performed GO analyses on those genes that were altered following HOPX expression in OSCC cells in vitro that were also transcriptionally deregulated in micro-dissected primary OSCCs16. Similarly, pathways related to cell proliferation, adhesion and migration were identified plus pathways associated with epithelial development and differentiation.…”

“…A similar GO analysis was performed on those genes down-regulated by HOPX in H376 and up-regulated in primary OSCCs ( C ) and those up-regulated by HOPX in H376 and down-regulated in tumours ( D ). Genes altered in H376/HOPX were compared with genes whose expression was altered in micro-dissected OSCCs (GSE35261 dataset16). …”

Expression and influence of Notch signaling in oral squamous cell carcinoma

“…Expression datasets of human cell line were excluded in the study. The included GEO datasets (GSE) are shown in Table 1 (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35).…”

Interferon-stimulated Gene 15 (ISG15) is a trigger for tumorigenesis and metastasis of hepatocellular carcinoma

“…Like other innate immune/stress response mediators, appropriately regulated ISG15 expression is associated with a tumor suppressor function, whereas the perturbation of ISG15 regulation is correlated with enhanced tumor progression and leads to aberrant cell signaling and malignant transformation [12, 21, 24, 25]. Unlike ubiquitin whose expression is more or less constant in all cells, the ISG15 protein is highly expressed in the majority of tumor cells.…”