IGFBP6 is a novel nasopharyngeal carcinoma prognostic biomarker
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Qiuyan Chen1,2,*, Siyuan Qin3,4,*, Yang Liu3,4, Minghuang Hong1,2, Chao-Nan Qian1,2, Evan T. Keller5, Jian Zhang3,4,6, Yi Lu3,4,6
1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
3Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China
4Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China
5Department of Urology and Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA
6Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
*These authors contributed equally to this work
Yi Lu, email: firstname.lastname@example.org
Keywords: IGFBP6, GSK3β, β-catenin, cyclin D1, nasopharyngeal carcinoma
Received: June 11, 2016 Accepted: September 01, 2016 Published: September 07, 2016
Insulin-like growth factor binding proteins (IGFBPs) play critical roles in carcinogenesis. This study assessed the impact of IGFBP6 on the progression of nasopharyngeal carcinoma (NPC). Using immunohistochemical analysis, we found that IGFBP6 was differentially expressed in primary malignant NPC tissues. Clinical samples were divided into two groups: IGFBP6(+) and IGFBP6(−). Five years of follow-up revealed that overall survival and distant metastasis-free survival rates were significantly higher in the IGFBP6(+) than IGFBP6(−) group. We also used real-time PCR, ELISA and western blot assays to measure IGFBP6 levels in five NPC cell lines (CNE1, CNE2, HONE1, HK1 and SUNE1). All the cell lines expressed IGFBP6, but at different levels, reflecting disease heterogeneity. In addition, exogenous expression of IGFBP6 inhibited CNE2 cell proliferation and invasion in vitro. IGFBP6 knockdown activated the GSK3β/β-catenin/cyclin D1 pathway and enhanced CNE2 tumor cell growth and metastasis in a mouse model. These results suggest that IGFBP6 may be an independent prognostic biomarker for NPC.
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