High-density lipoprotein cholesterol as a predictor of poor survival in patients with nasopharyngeal carcinoma

// Yan-Yan Liu 1, 2, # , Shao-Jun Lin 3, # , Yuan-Yuan Chen 4, # , Li-Na Liu 5 , Liu-Bin Bao 5 , Lin-Quan Tang 1 , Jing-Song Ou 6 , Zhi-Gang Liu 7 , Xiao-Zhong Chen 4 , Yan Xu 4 , Jun Ma 1 , Anthony T. Chan 8 , Ming Chen 4 , Yun-Fei Xia 1 , Wan-Li Liu 1 , Yi-Xin Zeng 1 , Hai-Qiang Mai 1 , Mu-Sheng Zeng 1 , Jian-Ji Pan 3, * , Xing Zhang 1, * 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 3 Department of Radiation Oncology, Fujian Provincial Cancer Hospital Affiliated to Fujian Medical University, Fuzhou, China 4 Department of Radiation Oncology, Zhejiang Cancer Hospital/Zhejiang Key Laboratory, Hangzhou, China 5 Department of Oncology, The Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China 6 Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 7 Department of Radiation Oncology, Hunan Provincial Tumor Hospital, Tumor Hospital Xiangya School of Medicine of Central South University, Changsha, China 8 Partner State Key Laboratory of Oncology in South China at Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong * These authors have contributed equally and share senior authorship # These authors have contributed equally to this work Correspondence to: Xing Zhang, email: zhangxing@sysucc.org.cn Keywords: high-density lipoprotein cholesterol, nasopharyngeal carcinoma, prognosis Received: November 22, 2015 Accepted: January 19, 2016 Published: February 03, 2016 ABSTRACT Purpose: We aimed to assess the prognostic value of pretreatment high density lipoprotein cholesterol (HDL-C) levels in patients with nasopharyngeal carcinoma (NPC) and investigate the possible biological effects of these lipoproteins on NPC cells in vitro . Experimental Design: We examined the prognostic value of pretreatment HDL-C levels in 2443 patients with non-metastatic NPC from three independent institutions. The Cox proportional hazard model and log-rank test were used to analyze the correlation between HDL-C levels and overall survival (OS). Cell growth, colony formation, and apoptotic assays were used to determine the biological functions of HDL on NPC cells in vitro . All of the statistical tests were two-sided. Results: OS was decreased in patients with high pretreatment HDL-C levels compared with those with low HDL-C levels ( P < 0.05). Similarly, a decreased OS was noted in advanced stage (stage III-IV), NPC patients with high pretreatment HDL-C levels ( P < 0.01). Multivariate analyses indicated that HDL-C was an independent prognostic factor associated with shorter OS in training cohorts. These findings were confirmed in both independent validation cohorts ( P < 0.01). In vitro experiments demonstrated that HDL could increase cell proliferation, invasion, and colony formation, which were largely dependent on the expression of its receptor SR-B1. Finally, HDL could enhance chemoresistance by protecting cancer cells from apoptosis. Conclusions: Pretreatment HDL-C is a poor prognostic factor for patients with NPC. This effect may be associated with the ability of HDL to enhance proliferation, colony formation, migration, and chemoresistance in NPC cells.