Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China

Weiyi Fang, Xin Li, Qingping Jiang, Zhen Liu, Huiling Yang, Shuang Wang, Siming Xie, Qiuzhen Liu, Tengfei Liu, Jing Huang, Weibing Xie, Zuguo Li, Yingdong Zhao, Ena Wang, Francesco M. Marincola, Kaitai Yao

Research output: Contribution to journalArticle

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Abstract

Background: The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated. Methods: Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry. Results: Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions asociated with cell growth, signal transduction and immune system activation. Conclusion: This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC.

Original languageEnglish
Article number32
JournalJournal of Translational Medicine
Volume6
DOIs
Publication statusPublished - 20 Jun 2008
Externally publishedYes

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Biomarkers
China
Genes
Tumor Suppressor Genes
Oncogenes
Tissue
Microarrays
Tumors
Vascular Endothelial Growth Factor B
RNA
Nasopharyngeal carcinoma
Search Engine
Signal transduction
Immune system
Automatic teller machines
Cell growth
Virus Diseases
Genetic Predisposition to Disease
Tumor Biomarkers
Search engines

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. / Fang, Weiyi; Li, Xin; Jiang, Qingping; Liu, Zhen; Yang, Huiling; Wang, Shuang; Xie, Siming; Liu, Qiuzhen; Liu, Tengfei; Huang, Jing; Xie, Weibing; Li, Zuguo; Zhao, Yingdong; Wang, Ena; Marincola, Francesco M.; Yao, Kaitai.

In: Journal of Translational Medicine, Vol. 6, 32, 20.06.2008.

Research output: Contribution to journalArticle

Fang, W, Li, X, Jiang, Q, Liu, Z, Yang, H, Wang, S, Xie, S, Liu, Q, Liu, T, Huang, J, Xie, W, Li, Z, Zhao, Y, Wang, E, Marincola, FM & Yao, K 2008, 'Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China', Journal of Translational Medicine, vol. 6, 32. https://doi.org/10.1186/1479-5876-6-32
Fang, Weiyi ; Li, Xin ; Jiang, Qingping ; Liu, Zhen ; Yang, Huiling ; Wang, Shuang ; Xie, Siming ; Liu, Qiuzhen ; Liu, Tengfei ; Huang, Jing ; Xie, Weibing ; Li, Zuguo ; Zhao, Yingdong ; Wang, Ena ; Marincola, Francesco M. ; Yao, Kaitai. / Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. In: Journal of Translational Medicine. 2008 ; Vol. 6.
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abstract = "Background: The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated. Methods: Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry. Results: Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions asociated with cell growth, signal transduction and immune system activation. Conclusion: This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC.",
author = "Weiyi Fang and Xin Li and Qingping Jiang and Zhen Liu and Huiling Yang and Shuang Wang and Siming Xie and Qiuzhen Liu and Tengfei Liu and Jing Huang and Weibing Xie and Zuguo Li and Yingdong Zhao and Ena Wang and Marincola, {Francesco M.} and Kaitai Yao",
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AU - Li, Xin

AU - Jiang, Qingping

AU - Liu, Zhen

AU - Yang, Huiling

AU - Wang, Shuang

AU - Xie, Siming

AU - Liu, Qiuzhen

AU - Liu, Tengfei

AU - Huang, Jing

AU - Xie, Weibing

AU - Li, Zuguo

AU - Zhao, Yingdong

AU - Wang, Ena

AU - Marincola, Francesco M.

AU - Yao, Kaitai

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N2 - Background: The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated. Methods: Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry. Results: Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions asociated with cell growth, signal transduction and immune system activation. Conclusion: This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC.

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