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. 2003 Jan;9(1):9-15.
doi: 10.3748/wjg.v9.i1.9.

Gene expression profiles at different stages of human esophageal squamous cell carcinoma

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Gene expression profiles at different stages of human esophageal squamous cell carcinoma

Jin Zhou et al. World J Gastroenterol. 2003 Jan.

Abstract

Aim: To characterize the gene expression profiles in different stages of carcinogenesis of esophageal epithelium.

Methods: A microarray containing 588 cancer related genes was employed to study the gene expression profile at different stages of esophageal squamous cell carcinoma including basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer. Principle component analysis was performed to search the genes which were important in carcinogenesis.

Results: More than 100 genes were up or down regulated in esophageal epithelial cells during the stages of basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer. Principle component analysis identified a set of genes which may play important roles in the tumor development. Comparison of expression profiles between these stages showed that some genes, such as P160ROCK, JNK2, were activated and may play an important role in early stages of carcinogenesis.

Conclusion: These findings provided an esophageal cancer-specific and stage-specific expression profiles, showing that complex alterations of gene expression underlie the development of malignant phenotype of esophageal cancer cells.

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Figures

Figure 1
Figure 1
Expression patterns of genes in esophageal tissue of normal, basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and advanced cancer. Total RNAs were isolated from these tissues, reverse-transcribed into 32P-labeled cDNAs and hybridized to AtlasTM Human Cancer cDNA expression arrays. A complete list of names and location of the arrayed gene can be found in the instruction manual and website from Clontech. Data was analyzed by AtlasImageTM 1.01 software. A, B, C, D, E, F showed hybridization result of normal cells, basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and advanced cancer; G, H, I, J, K showed the color charts indicating up-regulated genes with red, down-regulated genes with blue, and non-changed genes with green in the later 5 stages when compared to normal tissue; L, M, N, O, P showed the pathological image of normal, basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and advanced cancer respectively.
Figure 2
Figure 2
Validation of array data with RT-PCR: Rho8, Wnt 13, IL-1 beta, IL-1 receptor antagonist and cytokeratin 4 were chosen to further investigate the reliability of the array data using RT-PCR. The figures showed part of the RT-PCR results of five genes in cancer (designated T) and matched almost normal tissues(designated N). P means positive control.
Figure 3
Figure 3
Expression level of p160ROCK (3A) and JNK2 (3B) in 6 different stages, p160ROCK peaked its expression at stage of high-grade dysplasia and JNK2 peaked its expression at stage of carcinoma in situ. The column chart indicated expression levels of p160ROCK and JNK2 in stages of normal mucosa (designated normal), basal cell hyperplasia II (designated BCH), high grade dysplasia (designated Dys), squamous cell carcinoma in situ (designated CAIN), early cancer (designated ELCA) and late cancer (designated LaCa).

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