LOX Expression in Primary Nasopharyngeal Carcinoma: Correlation with Prognostic Parameters and Outcome

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Feb 17

PMID 26882568

Citations 8

Authors

Yi-Jun Hua

Hai-Yun Wang

Ling-Quan Tang

Qiu-Yan Chen

Jian-Yong Shao

Hai-Qiang Mai

Affiliations

Soon will be listed here.

Abstract

Lysyl oxidase (LOX) is an extracellular matrix-remodeling enzyme that plays important roles in tumor development and progression. To evaluate the prognostic value of LOX levels in primary nasopharyngeal carcinoma, we performed an immunohistochemical analysis using 233 tissue biopsy specimens from as many patients. We found that the extent of immunohistochemical LOX staining correlated inversely with the clinicopathological features and survival. High LOX expression correlated with decreases in 5-year survival, overall survival, distant metastasis-free survival and disease-free survival (p < 0.05). Cox regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5-year mortality for all patients (hazard ratio [HR], 1.670; 95% confidence interval [95% CI], 1.033-2.701 [p < .005]). Higher LOX expression was also an independent predictor of poor prognosis in patients with nasopharyngeal carcinoma. These findings suggest LOX may be a new biomarker predictive of NPC prognosis and may also be a useful treatment target.

Citing Articles

Nasopharyngeal Carcinoma and Its Microenvironment: Past, Current, and Future Perspectives.

Su Z, Siak P, Leong C, Cheah S Front Oncol. 2022; 12:840467.

PMID: 35311066 PMC: 8924466. DOI: 10.3389/fonc.2022.840467.

Lysyl oxidase impacts disease outcomes and correlates with global DNA hypomethylation in esophageal cancer.

Kalikawe R, Baba Y, Nomoto D, Okadome K, Miyake K, Eto K Cancer Sci. 2019; 110(12):3727-3737.

PMID: 31599475 PMC: 6890447. DOI: 10.1111/cas.14214.

A biomimetic 3D model of hypoxia-driven cancer progression.

Liverani C, De Vita A, Minardi S, Kang Y, Mercatali L, Amadori D Sci Rep. 2019; 9(1):12263.

PMID: 31439905 PMC: 6706452. DOI: 10.1038/s41598-019-48701-4.

Lysyl oxidase induces epithelial-mesenchymal transition and predicts intrahepatic metastasis of hepatocellular carcinoma.

Umezaki N, Nakagawa S, Yamashita Y, Kitano Y, Arima K, Miyata T Cancer Sci. 2019; 110(6):2033-2043.

PMID: 30919528 PMC: 6550133. DOI: 10.1111/cas.14010.

Inhibition of lysyl oxidase expression by dextran sulfate affects invasion and migration of gastric cancer cells.

Xu Y, Wang X, Huang Y, Ma Y, Jin X, Wang H Int J Mol Med. 2018; 42(5):2737-2749.

PMID: 30226558 PMC: 6192768. DOI: 10.3892/ijmm.2018.3855.

References

Lapointe J, Li C, Higgins J, van de Rijn M, Bair E, Montgomery K . Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A. 2004; 101(3):811-6. PMC: 321763. DOI: 10.1073/pnas.0304146101. View

Kagan H, Li W . Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem. 2003; 88(4):660-72. DOI: 10.1002/jcb.10413. View

Albinger-Hegyi A, Stoeckli S, Schmid S, Storz M, Iotzova G, Probst-Hensch N . Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC). Int J Cancer. 2009; 126(11):2653-62. DOI: 10.1002/ijc.24948. View

Stassar M, Devitt G, BROSIUS M, Rinnab L, Prang J, Schradin T . Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer. 2001; 85(9):1372-82. PMC: 2375251. DOI: 10.1054/bjoc.2001.2074. View

Erler J, Bennewith K, Nicolau M, Dornhofer N, Kong C, Le Q . Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 2006; 440(7088):1222-6. DOI: 10.1038/nature04695. View

Cox T, Bird D, Baker A, Barker H, Ho M, Lang G . LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res. 2013; 73(6):1721-32. PMC: 3672851. DOI: 10.1158/0008-5472.CAN-12-2233. View

Panchenko M, Stetler-Stevenson W, Trubetskoy O, Gacheru S, Kagan H . Metalloproteinase activity secreted by fibrogenic cells in the processing of prolysyl oxidase. Potential role of procollagen C-proteinase. J Biol Chem. 1996; 271(12):7113-9. DOI: 10.1074/jbc.271.12.7113. View

Kalogera-Fountzila A, Karanikolas D, Katodritis N, Samantas E, Sarafopoulos A, Ikonomou I . Prognostic factors and significance of the revised 6th edition of the AJCC classification in patients with locally advanced nasopharyngeal carcinoma. Strahlenther Onkol. 2006; 182(8):458-66. DOI: 10.1007/s00066-006-1538-4. View

Kagan H, Trackman P . Properties and function of lysyl oxidase. Am J Respir Cell Mol Biol. 1991; 5(3):206-10. DOI: 10.1165/ajrcmb/5.3.206. View

10.

Zhang Q, Jin X, Yang Z, Wei M, Zhu X, Wang P . Upregulated expression of LOX is a novel independent prognostic marker of worse outcome in gastric cancer patients after curative surgery. Oncol Lett. 2013; 5(3):896-902. PMC: 3576180. DOI: 10.3892/ol.2012.1092. View

11.

Wilgus M, Borczuk A, Stoopler M, Ginsburg M, Gorenstein L, Sonett J . Lysyl oxidase: a lung adenocarcinoma biomarker of invasion and survival. Cancer. 2011; 117(10):2186-91. DOI: 10.1002/cncr.25768. View

12.

Yoshizaki T, Miwa T, Furukawa M . Clinical evaluation of staging system for nasopharyngeal carcinoma: comparison of fourth and fifth editions of UICC TNM classification. Ann Otol Rhinol Laryngol. 2000; 109(12 Pt 1):1125-9. DOI: 10.1177/000348940010901208. View

13.

Ji F, Wang Y, Qiu L, Li S, Zhu J, Liang Z . Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer. Int J Oncol. 2013; 42(5):1578-88. PMC: 3661201. DOI: 10.3892/ijo.2013.1878. View

14.

Erler J, Bennewith K, Cox T, Lang G, Bird D, Koong A . Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell. 2008; 15(1):35-44. PMC: 3050620. DOI: 10.1016/j.ccr.2008.11.012. View

15.

Xu X, Wang B, Xu Y . Expression of lysyl oxidase in human osteosarcoma and its clinical significance: a tumor suppressive role of LOX in human osteosarcoma cells. Int J Oncol. 2013; 43(5):1578-86. DOI: 10.3892/ijo.2013.2067. View

16.

Payne S, Hendrix M, Kirschmann D . Paradoxical roles for lysyl oxidases in cancer--a prospect. J Cell Biochem. 2007; 101(6):1338-54. DOI: 10.1002/jcb.21371. View

17.

Molnar J, Fong K, He Q, Hayashi K, Kim Y, Fong S . Structural and functional diversity of lysyl oxidase and the LOX-like proteins. Biochim Biophys Acta. 2003; 1647(1-2):220-4. DOI: 10.1016/s1570-9639(03)00053-0. View

18.

Weise J, Rudolph P, Heiser A, Kruse M, Hedderich J, Cordes C . LOXL4 is a selectively expressed candidate diagnostic antigen in head and neck cancer. Eur J Cancer. 2008; 44(9):1323-31. DOI: 10.1016/j.ejca.2008.03.026. View

19.

Bertout J, Patel S, Simon M . The impact of O2 availability on human cancer. Nat Rev Cancer. 2008; 8(12):967-75. PMC: 3140692. DOI: 10.1038/nrc2540. View

20.

Li W, Nellaiappan K, Strassmaier T, Graham L, Thomas K, Kagan H . Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. Proc Natl Acad Sci U S A. 1997; 94(24):12817-22. PMC: 24221. DOI: 10.1073/pnas.94.24.12817. View