Bicluster and pathway enrichment analysis related to tumor progression of hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma is one of the most aggressive cancers with poor prognosis worldwide. Tumor progression remains a significant cause of high mortality in patients with hepatocellular carcinoma. However, the molecular mechanism underlying tumor progression of hepatocellular carcinoma has not been completely unraveled currently. The aim of this study was to gain insight into the molecular mechanisms of tumor progression of hepatocellular carcinoma.


METHODS
We performed microarray analysis on 24 tissue specimens obtained at the time of surgical resection or liver transplantation from 24 patients with hepatocellular carcinoma downloaded from the Gene Expression Omnibus database.


RESULTS
Our analysis indicated that several differentially expressed genes might play crucial roles in the progression of hepatocellular carcinoma, such as GADD45G, SPTBN1, CDC27, TPD52 and INSIG1. GADD45G and SPTBN1 not only contribute to tumor progression in hepatocellular carcinoma, but also correlate with poor prognosis in esophageal squamous cell carcinoma and pancreatic cancer respectively. Futhermore, we performed pathway enrichment analysis and found enriched pathways, including "Proteasome", "Alanine, aspartate and glutamate metabolism", "TGF-beta signaling pathway", "Wnt signaling pathway", and so on.


CONCLUSIONS
Our findings confirmed the presence of multiple molecular alterations during tumor progression and indicated the differentially expressed genes might be involved in tumor progression though multiple pathways. Genes GADD45G and SPTBN1 might correlate with poor prognosis in hepatocellular carcinoma as has already been shown for other malignancies of the gastrointestinal tract.
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. mengzhq@gmail.com.
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Wang
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Feng
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Meng
D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D016000:Cluster Analysis; D030541:Databases, Genetic; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D040081:Protein Array Analysis / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D016212:Transforming Growth Factor beta