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Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer
Open accessAbstract
Background & Aims Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. Methods cDNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplstic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n=450) and a validation set (n=502) of samples from gastric cancer patients. Results Compared to normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%–50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and a validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. Conclusion We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was upregulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early-stage gastric cancer.
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More powerful procedures for multiple significance testing
Hochberg, Y., & Benjamini, Y. (1990) · Statistics in Medicine · doi:10.1002/sim.4780090710 · Cited by 2,715
Gene Expression Profile of Gastric Carcinoma
Oue, N., Hamai, Y., Mitani, Y., Matsumura, S., Oshimo, Y., Aung, P. P., Kuraoka, K., Nakayama, H., & Yasui, W. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3514 · Cited by 265
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Zhang, P., Yang, M., Zhang, Y., Xiao, S., Lai, X., Tan, A., Du, S., & Li, S. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.052 · Cited by 478
Lei, Z., Tan, I. B., Das, K., Deng, N., Zouridis, H., Pattison, S., Chua, C., Feng, Z., Guan, Y. K., Ooi, C. H., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.010 · Cited by 458
Zhang, M., Hu, S., Min, M., Ni, Y., Lu, Z., Sun, X., Wu, J., Liu, B., Ying, X., & Liu, Y. (2021) · Gut · doi:10.1136/gutjnl-2019-320368 · Cited by 339
Yu, S., Yang, M., Lim, K.-M., Cho, Y., Kim, H., Lee, K., Jeong, S.-H., Coffey, R. J., Goldenring, J. R., & Nam, K. T. (2018) · The American Journal of Pathology · doi:10.1016/j.ajpath.2018.08.006 · Cited by 19
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Metadata
- Authors
- Lee, H., Nam, K. T., Park, H. S., Kim, M. A., LaFleur, B. J., Aburatani, H., Yang, H., Kim, W. H., & Goldenring, J. R.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 139
- Issue
- 1
- Pages
- 213-225.e3
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2148553058
- Cited by
- 158
- References
- 2
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Lee, H., Nam, K. T., Park, H. S., Kim, M. A., LaFleur, B. J., Aburatani, H., Yang, H., Kim, W. H., & Goldenring, J. R. (2010). Gene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer. Gastroenterology. https://doi.org/10.1053/j.gastro.2010.04.008
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