Abstract
The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. Serum lipids and lipoproteins have been reported to be associated with prognosis in some cancers, but it has not been studied in metastatic NPC. The aim of this study was to evaluate whether serum lipid and lipoproteins could predict the prognosis of metastatic NPC patients. Eight hundred and seven patients with metastatic NPC were analyzed retrospectively, and the values of serum lipids and lipoproteins at baseline were retrieved. Receiver operating characteristic curve analysis and univariate and multivariate Cox proportional hazards analyses were used to evaluate the associations of serum lipids and lipoproteins with overall survival (OS). Univariate analysis revealed that higher values of baseline cholesterol (≥4.655 mmol/L), baseline high-density lipoprotein cholesterol (≥0.965 mmol/L), and baseline apolipoprotein A-I (ApoA-I) (≥1.065 g/L) were significantly associated with superior OS (p < 0.001), respectively. Multivariate Cox proportional hazard analysis showed that higher ApoA-I level (vs. lower ApoA-I level, HR 0.64, 95 % CI 0.52–0.80, p < 0.001) was an independent protective factor against progression. In addition, higher body mass index, earlier N stages, single lesion, and absence of liver metastasis were also revealed to be independent protective factors. In conclusion, the elevated baseline ApoA-I level may predict those patients likely to have a favorable OS.
Similar content being viewed by others
References
Lee AW, Sze WM, Au JS, Leung SF, Leung TW, Chua DT, Zee BC, Law SC, Teo PM, Tung SY, Kwong DL, Lau WH. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2005;61:1107–16.
Hui EP, Leung SF, Au JS, Zee B, Tung S, Chua D, Sze WM, Law CK, Leung TW, Chan AT. Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group. Cancer. 2004;101:300–6.
Bensouda Y, Kaikani W, Ahbeddou N, Rahhali R, Jabri M, Mrabti H, Boussen H, Errihani H. Treatment for metastatic nasopharyngeal carcinoma. Eur Ann Otorhinolaryngol Head Neck Dis. 2011;128:79–85.
Razak AR, Siu LL, Liu FF, Ito E, O’Sullivan B, Chan K. Nasopharyngeal carcinoma: the next challenges. Eur J Cancer. 2010;46:1967–78.
Teo PM, Kwan WH, Lee WY, Leung SF, Johnson PJ. Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma. Cancer. 1996;77:2423–31.
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med. 2003;348:1625–38.
Michalaki V, Koutroulis G, Syrigos K, Piperi C, Kalofoutis A. Evaluation of serum lipids and high-density lipoprotein subfractions (HDL2, HDL3) in postmenopausal patients with breast cancer. Mol Cell Biochem. 2005;268:19–24.
Gaziano JM, Hennekens CH. Dietary fat and risk of prostate cancer. J Natl Cancer Inst. 1995;87:1427–8.
van Duijnhoven FJ, Bueno-De-Mesquita HB, Calligaro M, Jenab M, Pischon T, Jansen EH, Frohlich J, Ayyobi A, Overvad K, Toft-Petersen AP, Tjonneland A, Hansen L, Boutron-Ruault MC, Clavel-Chapelon F, Cottet V, Palli D, Tagliabue G, Panico S, Tumino R, Vineis P, Kaaks R, Teucher B, Boeing H, Drogan D, Trichopoulou A, Lagiou P, Dilis V, Peeters PH, Siersema PD, Rodriguez L, Gonzalez CA, Molina-Montes E, Dorronsoro M, Tormo MJ, Barricarte A, Palmqvist R, Hallmans G, Khaw KT, Tsilidis KK, Crowe FL, Chajes V, Fedirko V, Rinaldi S, Norat T, Riboli E. Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition. Gut. 2011;60:1094–102.
Siemianowicz K, Gminski J, Stajszczyk M, Wojakowski W, Goss M, Machalski M, Telega A, Brulinski K, Magiera-Molendowska H. Serum total cholesterol and triglycerides levels in patients with lung cancer. Int J Mol Med. 2000;5:201–5.
Tamura T, Inagawa S, Hisakura K, Enomoto T, Ohkohchi N. Evaluation of serum high-density lipoprotein cholesterol levels as a prognostic factor in gastric cancer patients. J Gastroenterol Hepatol. 2012;27:1635–40.
Wang X, Dai S, Zhang Z, Liu L, Wang J, Xiao X, He D, Liu B. Characterization of apolipoprotein A-I as a potential biomarker for cholangiocarcinoma. Eur J Cancer Care (Engl). 2009;18:625–35.
Zeng Y, Zhang LG, Wu YC, Huang YS, Huang NQ, Li JY, Wang YB, Jiang MK, Fang Z, Meng NN. Prospective studies on nasopharyngeal carcinoma in Epstein-Barr virus IgA/VCA antibody-positive persons in Wuzhou City. China Int J Cancer. 1985;36:545–7.
Xiao WW, Huang SM, Han F, Wu SX, Lu LX, Lin CG, Deng XW, Lu TX, Cui NJ, Zhao C. Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results of a phase 2 study. Cancer. 2011;117:1874–83.
Chen MY, Jiang R, Guo L, Zou X, Liu Q, Sun R, Qiu F, Xia ZJ, Huang HQ, Zhang L, Hong MH, Mai HQ, Qian CN. Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis. Chin J Cancer. 2013;32:604–13.
Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011;80:661–8.
Pan CC, Lu J, Yu JR, Chen P, Li W, Huang ZL, Zhao M, Huang ZM, Xia YF, Wu YH, Wu PH. Challenges in the modification of the M1 stage of the TNM staging system for nasopharyngeal carcinoma: a study of 1027 cases and review of the literature. Exp Ther Med. 2012;4:334–8.
Brewer HJ, Fairwell T, LaRue A, Ronan R, Houser A, Bronzert TJ. The amino acid sequence of human APOA-I, an apolipoprotein isolated from high density lipoproteins. Biochem Biophys Res Commun. 1978;80:623–30.
Wasan KM, Brocks DR, Lee SD, Sachs-Barrable K, Thornton SJ. Impact of lipoproteins on the biological activity and disposition of hydrophobic drugs: implications for drug discovery. Nat Rev Drug Discov. 2008;7:84–99.
Yui Y, Aoyama T, Morishita H, Takahashi M, Takatsu Y, Kawai C. Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I. J Clin Invest. 1988;82:803–7.
Yui Y, Aoyama T, Morishita H, Takahashi M, Takatsu Y, Kawai C. Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I. J Clin Invest. 1988;82:803–7.
Zhang Z, Bast RJ, Yu Y, Li J, Sokoll LJ, Rai AJ, Rosenzweig JM, Cameron B, Wang YY, Meng XY, Berchuck A, Van Haaften-Day C, Hacker NF, de Bruijn HW, van der Zee AG, Jacobs IJ, Fung ET, Chan DW. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res. 2004;64:5882–90.
Ehmann M, Felix K, Hartmann D, Schnolzer M, Nees M, Vorderwulbecke S, Bogumil R, Buchler MW, Friess H. Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling. Pancreas. 2007;34:205–14.
Chang SJ, Hou MF, Tsai SM, Wu SH, Hou LA, Ma H, Shann TY, Wu SH, Tsai LY. The association between lipid profiles and breast cancer among Taiwanese women. Clin Chem Lab Med. 2007;45:1219–23.
Lane DM, Boatman KK, McConathy WJ. Serum lipids and apolipoproteins in women with breast masses. Breast Cancer Res Treat. 1995;34:161–9.
Zur HH, Schulte-Holthausen H, Klein G, Henle W, Henle G, Clifford P, Santesson L. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature. 1970;228:1056–8.
Eliopoulos AG, Stack M, Dawson CW, Kaye KM, Hodgkin L, Sihota S, Rowe M, Young LS. Epstein-Barr virus-encoded LMP1 and CD40 mediate IL-6 production in epithelial cells via an NF-kappaB pathway involving TNF receptor-associated factors. Oncogene. 1997;14:2899–916.
Crowl RM, Stoller TJ, Conroy RR, Stoner CR. Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. J Biol Chem. 1991;266:2647–51.
Tietge UJ, Maugeais C, Cain W, Grass D, Glick JM, de Beer FC, Rader DJ. Overexpression of secretory phospholipase A(2) causes rapid catabolism and altered tissue uptake of high density lipoprotein cholesteryl ester and apolipoprotein A-I. J Biol Chem. 2000;275:10077–84.
Tietge UJ, Maugeais C, Lund-Katz S, Grass D, DeBeer FC, Rader DJ. Human secretory phospholipase A2 mediates decreased plasma levels of HDL cholesterol and apoA-I in response to inflammation in human apoA-I transgenic mice. Arterioscler Thromb Vasc Biol. 2002;22:1213–8.
Zamanian-Daryoush M, Lindner D, Tallant TC, Wang Z, Buffa J, Klipfell E, Parker Y, Hatala D, Parsons-Wingerter P, Rayman P, Yusufishaq MS, Fisher EA, Smith JD, Finke J, DiDonato JA, Hazen SL. The cardioprotective protein apolipoprotein A1 promotes potent anti-tumorigenic effects. J Biol Chem. 2013;288:21237–52.
Honn KV, Cicone B, Skoff A. Prostacyclin: a potent antimetastatic agent. Science. 1981;212:1270–2.
Meyer F, Fortin A, Gelinas M, Nabid A, Brochet F, Tetu B, Bairati I. Health-related quality of life as a survival predictor for patients with localized head and neck cancer treated with radiation therapy. J Clin Oncol. 2009;27:2970–6.
Shen GP, Xu FH, He F, Ruan HL, Cui C, Chen LZ, Zeng YX, Jia WH. Pretreatment lifestyle behaviors as survival predictors for patients with nasopharyngeal carcinoma. PLoS ONE. 2012;7:e36515.
Patel PS, Shah MH, Jha FP, Raval GN, Rawal RM, Patel MM, Patel JB, Patel DD. Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions. Indian J Cancer. 2004;41:25–31.
Cambien F, Ducimetiere P, Richard J. Total serum cholesterol and cancer mortality in a middle-aged male population. Am J Epidemiol. 1980;112:388–94.
Acknowledgments
Supported by Sun Yat-Sen University Clinical Re 5010 Program (201310) and National Natural Science Foundation of China (Grants No. 81071890).
Conflict of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Additional information
Rou Jiang, Zhong-Han Yang, and Dong-Hua Luo have contributed equally to this study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
12032_2014_80_MOESM1_ESM.tif
Figure S1. Receiver Operating Characteristic (ROC) curve analyses of baseline serum lipid and lipoprotein levels, weight, height, and BMI cutoff points for Overall Survival (OS) analyses. ROC curve analyses to determine cutoff levels for triglyceride (A), cholesterol (B), HDL-C(C), LDL-C(D), ApoA-I (E), Apo-B (F), height (G), weight (H), and BMI (I). The triglyceride, cholesterol, HDL-C, LDL-C, ApoA-I, ApoB, height, weight, and BMI cutoff points for OS analyses were 0.955 mmol/L, 4.655 mmol/L, 0.965 mmol/L, 2.545 mmol/L, 1.065 g/L, 1.155 g/L, 164.25 cm, 57.25 kg, and 20.735 kg/m2, respectively. (TIFF 1430 kb)
Rights and permissions
About this article
Cite this article
Jiang, R., Yang, ZH., Luo, DH. et al. Elevated apolipoprotein A-I levels are associated with favorable prognosis in metastatic nasopharyngeal carcinoma. Med Oncol 31, 80 (2014). https://doi.org/10.1007/s12032-014-0080-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12032-014-0080-y