LTBP2 is a Prognostic Marker in Head and Neck Squamous Cell Carcinoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jun 10

PMID 27281608

Citations 12

Authors

Liang Han

Ming Ming Tang

Xinjiang Xu

Bin Jiang

Jianfei Huang

Xingmei Feng

Jianfeng Qiang

Affiliations

Soon will be listed here.

Abstract

Latent transforming growth factor (TGF)-beta binding protein 2 (LTBP2) belongs to the fibrillin/LTBP extracellular matrix glycoprotein superfamily. It plays vital roles in tumorigenesis through regulating TGFβ activity, elastogenesis and maintenance of the extracellular matrix (ECM) structure. In this study, we determined the expression levels of LTBP2 mRNA and protein in head and neck squamous cell carcinoma (HNSCC) tissues and adjacent normal tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC) respectively. LTBP2 protein levels in cancer tissues were correlated with HNSCC patients' clinical characteristics and overall survival. Both LTBP2 mRNA and protein levels were significantly higher in HNSCC tissues than in adjacent normal tissues. High LTBP2 protein level was associated with lymph node metastasis and higher pTNM stages. High LTBP2 protein level is an independent prognostic marker in HNSCC. Our data suggest that LTBP2 acts as an oncogene in HNSCC development and progression. Detection of LTBP2 expression could be a useful prognosis marker and targeting LTBP2 may represent a novel strategy for cancer treatment through regulating activities of TGFβ.

Citing Articles

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Multi-organ phenotypes in mice lacking latent TGFβ binding protein 2 (LTBP2).

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LTBP2 Knockdown Promotes Ferroptosis in Gastric Cancer Cells through p62-Keap1-Nrf2 Pathway.

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Expression and clinical significance of latent-transforming growth factor beta-binding protein 2 in primary hepatocellular carcinoma.

Chen J, Gao G, Wang H, Ye X, Zhou J, Lin J Medicine (Baltimore). 2019; 98(39):e17216.

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High Expression of LTBP2 Contributes to Poor Prognosis in Colorectal Cancer Patients and Correlates with the Mesenchymal Colorectal Cancer Subtype.

Huang Y, Wang G, Zhao C, Geng R, Zhang S, Wang W Dis Markers. 2019; 2019:5231269.

PMID: 30956730 PMC: 6431450. DOI: 10.1155/2019/5231269.

References

Oklu R, Hesketh R . The latent transforming growth factor beta binding protein (LTBP) family. Biochem J. 2000; 352 Pt 3:601-10. PMC: 1221494. View

da Costa A, Plymoth A, Santos-Silva D, Ortiz-Cuaran S, Camey S, Guilloreau P . Osteopontin and latent-TGF β binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma. Int J Cancer. 2014; 136(1):172-81. PMC: 4617682. DOI: 10.1002/ijc.28953. View

Gatta G, Botta L, Sanchez M, Anderson L, Pierannunzio D, Licitra L . Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study. Eur J Cancer. 2015; 51(15):2130-2143. DOI: 10.1016/j.ejca.2015.07.043. View

Detre S, Saclani Jotti G, Dowsett M . A "quickscore" method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995; 48(9):876-8. PMC: 502883. DOI: 10.1136/jcp.48.9.876. View

Jarvinen A, Autio R, Kilpinen S, Saarela M, Leivo I, Grenman R . High-resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx. Genes Chromosomes Cancer. 2008; 47(6):500-9. DOI: 10.1002/gcc.20551. View

Vehvilainen P, Hyytiainen M, Keski-Oja J . Latent transforming growth factor-beta-binding protein 2 is an adhesion protein for melanoma cells. J Biol Chem. 2003; 278(27):24705-13. DOI: 10.1074/jbc.M212953200. View

Xu Y, Wang C, Zhang Y, Jia L, Huang J . Overexpression of MAGE-A9 Is Predictive of Poor Prognosis in Epithelial Ovarian Cancer. Sci Rep. 2015; 5:12104. PMC: 4502509. DOI: 10.1038/srep12104. View

Saharinen J, Hyytiainen M, Taipale J, Keski-Oja J . Latent transforming growth factor-beta binding proteins (LTBPs)--structural extracellular matrix proteins for targeting TGF-beta action. Cytokine Growth Factor Rev. 2000; 10(2):99-117. DOI: 10.1016/s1359-6101(99)00010-6. View

Rai K, Akdemir K, Kwong L, Fiziev P, Wu C, Keung E . Dual Roles of RNF2 in Melanoma Progression. Cancer Discov. 2015; 5(12):1314-27. PMC: 4670809. DOI: 10.1158/2159-8290.CD-15-0493. View

10.

Todorovic V, Rifkin D . LTBPs, more than just an escort service. J Cell Biochem. 2012; 113(2):410-8. PMC: 3254144. DOI: 10.1002/jcb.23385. View

11.

Lu C, Wang X, Zhu H, Feng J, Ni S, Huang J . Over-expression of ROR2 and Wnt5a cooperatively correlates with unfavorable prognosis in patients with non-small cell lung cancer. Oncotarget. 2015; 6(28):24912-21. PMC: 4694803. DOI: 10.18632/oncotarget.4701. View

12.

Kan R, Shuen W, Lung H, Cheung A, Dai W, Kwong D . NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells. PLoS One. 2015; 10(5):e0127239. PMC: 4431814. DOI: 10.1371/journal.pone.0127239. View

13.

Raghupathy R, Hui E, Chan A . Epstein-Barr virus as a paradigm in nasopharyngeal cancer: from lab to clinic. Am Soc Clin Oncol Educ Book. 2014; :149-53. DOI: 10.14694/EdBook_AM.2014.34.149. View

14.

Wyss A, Hashibe M, Chuang S, Lee Y, Zhang Z, Yu G . Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Am J Epidemiol. 2013; 178(5):679-90. PMC: 3755640. DOI: 10.1093/aje/kwt029. View

15.

Ren Y, Lu H, Zhao D, Ou Y, Yu K, Gu J . LTPB2 acts as a prognostic factor and promotes progression of cervical adenocarcinoma. Am J Transl Res. 2015; 7(6):1095-105. PMC: 4532742. View

16.

Robertson I, Horiguchi M, Zilberberg L, Dabovic B, Hadjiolova K, Rifkin D . Latent TGF-β-binding proteins. Matrix Biol. 2015; 47:44-53. PMC: 4844006. DOI: 10.1016/j.matbio.2015.05.005. View

17.

Tong W, Wierda W, Lin E, Kuang S, Bekele B, Estrov Z . Genome-wide DNA methylation profiling of chronic lymphocytic leukemia allows identification of epigenetically repressed molecular pathways with clinical impact. Epigenetics. 2010; 5(6):499-508. PMC: 3322493. DOI: 10.4161/epi.5.6.12179. View

18.

Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S . Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res. 1999; 18(6B):4779-86. View

19.

Taipale J, Saharinen J, Keski-Oja J . Extracellular matrix-associated transforming growth factor-beta: role in cancer cell growth and invasion. Adv Cancer Res. 1998; 75:87-134. DOI: 10.1016/s0065-230x(08)60740-x. View

20.

Chan S, Ko J, Chan K, Chan Y, Tao Q, Hyytiainen M . The ECM protein LTBP-2 is a suppressor of esophageal squamous cell carcinoma tumor formation but higher tumor expression associates with poor patient outcome. Int J Cancer. 2010; 129(3):565-73. DOI: 10.1002/ijc.25698. View