J Cancer 2014; 5(7):525-536. doi:10.7150/jca.9207

Research Paper

Quantitative iTRAQ LC-MS/MS Proteomics Reveals Transcription Factor Crosstalk and Regulatory Networks in Hypopharyngeal Squamous Cell Carcinoma

Gangcai Zhu1,2, Gengming Cai3, Yong Liu1,2, Haolei Tan1,2, Changyun Yu1,2, Meiling Huang1,2, Ming Wei1,2, She Li1,2, Xiangning Cui1,2, Donghai Huang1,2, Yongquan Tian1,2, Xin Zhang1,2✉

1. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan, China.
2. Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, China.
3. Department of Otolaryngology Head and Neck Surgery, first hospital of Quanzhou, Fujian Medical University, Quanzhou 362002, Fujian, China.

Abstract

To date, no effective therapeutic treatments have been developed for hypopharyngeal squamous cell carcinoma (HPSCC), a disease that has a five-year survival rate of approximately 31% because of its late diagnosis and aggressive nature. Despite recent improvements in diagnostic methods, there are no effective measures to prevent or detect HPSCC in an early stage. The goal of the current study was to identify molecular biomarkers and networks that can facilitate the speedy identification of HPSCC patients who could benefit from individualized treatment. Isobaric tags for relative and absolute quantification (iTRAQ) labeling was employed with two-dimensional liquid chromatography-tandem mass spectrometry to identify quantitatively the differentially expressed proteins among three types of HPSCC disease stages. The iTRAQ results were evaluated by literature searches and western blot analysis. For example, FUBP1, one of 412 proteins with significantly altered expression profiles, was confirmed to have elevated expression in fresh HPSCC tissues. Integrin-mediated cell matrix adhesion and actin filament-inducing cytoskeleton remodeling were the cellular events that were the most relevant to HPSCC tumorigenesis and the metastatic process. The construction of transcriptional regulation networks led to the identification of key transcriptional regulators of tumor development and lymph node metastasis of HPSCC, including Sp1, c-Myc and p53. Additionally, our study indicated that the interactions among Sp1, c-Myc and p53 may play vital roles in the carcinogenesis and metastasis of HPSCC.

Keywords: Proteomics analysis, Metastasis, Hypopharyngeal squamous cell carcinoma, Transcription factor network, iTRAQ, Carcinogenesis.

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How to cite this article:
Zhu G, Cai G, Liu Y, Tan H, Yu C, Huang M, Wei M, Li S, Cui X, Huang D, Tian Y, Zhang X. Quantitative iTRAQ LC-MS/MS Proteomics Reveals Transcription Factor Crosstalk and Regulatory Networks in Hypopharyngeal Squamous Cell Carcinoma. J Cancer 2014; 5(7):525-536. doi:10.7150/jca.9207. Available from http://www.jcancer.org/v05p0525.htm