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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Serum low-density lipoprotein and low-density lipoprotein expression level at diagnosis are favorable prognostic factors in patients with small-cell lung cancer (SCLC)

Authors: Ting Zhou, Jianhua Zhan, Wenfeng Fang, Yuanyuan Zhao, Yunpeng Yang, Xue Hou, Zhonghan Zhang, Xiaobo He, Yaxiong Zhang, Yan Huang, Li Zhang

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Patients with small-cell lung cancer (SCLC) patients demonstrate varied survival outcomes. Previous studies have reported that lipoproteins are associated with prognosis in various cancers; however, the role of low-density lipoprotein (LDL) and low-density lipoprotein- cholesterol (LDLR) in patients with SCLC has not been studied.

Methods

In this study, the impact of LDL and LDLR on the prognosis of SCLC patients was evaluated. A total of 601 patients with SCLC were retrospectively evaluated, in which 198 patients had adequate tissues for immunohistochemistry, and serum LDL and LDLR expression levels at baseline were tested. X-tile tool, and univariate and multivariate Cox analysis were used to assess the association between LDL, LDLR and overall survival (OS).

Results

Univariate analysis demonstrated that a lower LDL level was significantly associated with superior OS (P = 0.037). Similarly, LDLR also significantly predicted OS (P = 0.003). Multivariate Cox analyses confirmed that lower LDL and LDLR expression was independent prognostic factors associated with longer OS (P = 0.019 and P = 0.027, respectively).

Conclusions

This study showed that both LDL and LDLR are prognostic indexes for survival in patients with SCLC. Patients with high LDL or LDLR expression level may benefit from treatment that modulates lipoprotein combined with platinum-based chemotherapy.
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Literature
1.
2.
3.
Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24(28):4539–44.CrossRefPubMed
4.
5.
Lally BE, Urbanic JJ, Blackstock AW, Miller AA, Perry MC. Small cell lung cancer: have we made any progress over the last 25 years? Oncologist. 2007;12(9):1096–104.CrossRefPubMed
6.
Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28(31):4706–13.CrossRefPubMed
7.
Gralla RJ. Quality-of-life considerations in patients with advanced lung cancer: effect of topotecan on symptom palliation and quality of life. Oncologist. 2004;9(Suppl 6):14–24.CrossRefPubMed
8.
Sugiyama T, Hirose T, Hosaka T, Kusumoto S, Nakashima M, Yamaoka T, et al. Effectiveness of intensive follow-up after response in patients with small cell lung cancer. Lung Cancer. 2008;59(2):255–61.CrossRefPubMed
9.
Hann CL, Rudin CM. Management of small-cell lung cancer: incremental changes but hope for the future. Oncology. 2008;22:1486–92.PubMedPubMedCentral
10.
Brameshuber M, Sevcsik E, Rossboth BK, Manner C, Deigner HP, Peksel B, et al. Oxidized phospholipids inhibit the formation of cholesterol-dependent plasma membrane nanoplatforms. Biophys J. 2016;110(1):205–13.CrossRefPubMedPubMedCentral
11.
Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005;115(4):959–68.CrossRefPubMedPubMedCentral
12.
Cruz PM, Mo H, McConathy WJ, Sabnis N, Lacko AG. The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics. Front Pharmacol. 2013;4:119.CrossRefPubMedPubMedCentral
13.
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7(1):11–20.CrossRefPubMed
14.
Lee BH, Taylor MG, Robinet P, Smith JD, Alermus JB, Sehayek E, et al. Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1. Cancer Res. 2013;73(3):1211–8.CrossRefPubMed
15.
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.CrossRefPubMed
16.
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(1–2):19–24.CrossRefPubMed
17.
Jiang R, Yang ZH, Luo DH, Guo L, Sun R, Chen QY, et al. Elevated apolipoprotein A-I levels are associated with favorable prognosis in metastatic nasopharyngeal carcinoma. Med Oncol. 2014;31(8):80.CrossRefPubMed
18.
19.
Jeon JH, Kim SK, Kim HJ, Chang J, Ahn CM, Chang YS. Lipid raft modulation inhibits NSCLC cell migration through delocalization of the focal adhesion complex. Lung Cancer. 2010;69(2):165–71.CrossRefPubMed
20.
Reverter M, Rentero C, Garcia-Melero A, Hoque M, de Muga SV, Alvarez-Guaita A, et al. Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries. Cell Rep. 2014;7(3):883–97.CrossRefPubMed
21.
Hirsch HA, Iliopoulos D, Joshi A, Zhang Y, Jaeger SA, Bulyk M, et al. A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases. Cancer Cell. 2010;17(4):348–61.CrossRefPubMedPubMedCentral
22.
Damiano MG, Mutharasan RK, Tripathy S, McMahon KM, Thaxton CS. Templated high density lipoprotein nanoparticles as potential therapies and for molecular delivery. Adv Drug Deliv Rev. 2013;65(5):649–62.CrossRefPubMed
23.
Notarnicola M, Messa C, Orlando A, D'Attoma B, Tutino V, Rivizzigno R, et al. Effect of genistein on cholesterol metabolism-related genes in a colon cancer cell line. Genes Nutr. 2008;3(1):35–40.CrossRefPubMedPubMedCentral
24.
Guillaumond F, Bidaut G, Ouaissi M, Servais S, Gouirand V, Olivares O, et al. Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. Proc Natl Acad Sci U S A. 2015;112(8):2473–8.CrossRefPubMedPubMedCentral
25.
McCarty KS, Szabo E, Flowers JL, Cox EB, Leight GS, Miller L, et al. Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res. 1986;46(8 Suppl):4244s–8s.PubMed
26.
Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252–9.CrossRefPubMed
27.
Patel PS, Shah MH, Jha FP, Raval GN, Rawal RM, Patel MM, et al. Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions. Indian J Cancer. 2004;41(1):25–31.PubMed
28.
Girotti AW, Korytowski W. Cholesterol as a natural probe for free radical-mediated lipid peroxidation in biological membranes and lipoproteins. J Chromatogr B. 2016;1019:202–9.CrossRef
29.
Muntoni S, Atzori L, Mereu R, Satta G, Macis MD, Congia M, et al. Serum lipoproteins and cancer. Nutr Metab Cardiovasc Dis. 2009;19(3):218–25.CrossRefPubMed
30.
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(10):1635–40.CrossRefPubMed
31.
Danilo C, Frank PG. Cholesterol and breast cancer development. Curr Opin Pharmacol. 2012;12(6):677–82.CrossRefPubMed
32.
Saito N, Sairenchi T, Irie F, Iso H, Iimura K, Watanabe H, et al. Low serum LDL cholesterol levels are associated with elevated mortality from liver cancer in Japan: the Ibaraki prefectural health study. Tohoku J Exp Med. 2013;229(3):203–11.CrossRefPubMed
33.
Santos C, Fonseca I, Dias S, de Almeida JM. Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression. BMC Cancer. 2014;14(1):132.CrossRef
34.
Liu YL, Qian HX, Qin L, Zhou XJ, Zhang B. Serum LDL-C and LDL-C/HDL-C ratio are positively correlated to lymph node stages in males with colorectal cancer. Hepato-Gastroenterol. 2011;58(106):383–7.
35.
Migita T, Ruiz S, Fornari A, Fiorentino M, Priolo C, Zadra G, et al. Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst. 2009;101(7):519–32.CrossRefPubMedPubMedCentral
36.
Jiang L, Jiang S, Lin Y, Yang H, Zhao Z, Xie Z. Combination of body mass index and oxidized low density lipoprotein receptor 1 in prognosis prediction of patients with squamous non-small cell lung cancer. Oncotarget. 2015;6(26):22072–80.CrossRefPubMedPubMedCentral
37.
Harisa GI, Alanazi FK. Low density lipoprotein bionanoparticles: from cholesterol transport to delivery of anti-cancer drugs. Saudi Pharmaceutical J. 2014;22(6):504–15.CrossRef
Metadata
Title
Serum low-density lipoprotein and low-density lipoprotein expression level at diagnosis are favorable prognostic factors in patients with small-cell lung cancer (SCLC)
Authors
Ting Zhou
Jianhua Zhan
Wenfeng Fang
Yuanyuan Zhao
Yunpeng Yang
Xue Hou
Zhonghan Zhang
Xiaobo He
Yaxiong Zhang
Yan Huang
Li Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3239-z

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