Decreased DC‑SIGNR expression in hepatocellular carcinoma predicts poor patient prognosis

Xia,Hai‑Bing; Wang,Hui‑Ju; Song,Shu‑Shu; Zhang,Jun‑Gang; He,Xiang‑Lei; Hu,Zhi‑Ming; Zhang,Cheng‑Wu; Huang,Dong‑Sheng; Mou,Xiao‑Zhou

doi:10.3892/ol.2019.11074

Decreased DC‑SIGNR expression in hepatocellular carcinoma predicts poor patient prognosis

Authors:
- Hai‑Bing Xia
- Hui‑Ju Wang
- Shu‑Shu Song
- Jun‑Gang Zhang
- Xiang‑Lei He
- Zhi‑Ming Hu
- Cheng‑Wu Zhang
- Dong‑Sheng Huang
- Xiao‑Zhou Mou
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Affiliations: Department of Hepatobiliary Surgery, First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang 311200, P.R. China, Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, Zhejiang 310014, P.R. China
Published online on: November 11, 2019 https://doi.org/10.3892/ol.2019.11074
Pages: 69-76
Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dendritic cell‑specific intercellular adhesion molecule‑grabbing non‑integrin‑related protein (DC‑SIGNR) is a transmembrane receptor primarily involved in pathogen recognition by the innate immune system, with particular importance for viral recognition. DC‑SIGNR may also be associated with tumorigenesis. The aim of the present study was to investigate the association between DC‑SIGNR expression, development of hepatocellular carcinoma (HCC), and clinicopathological features. Immunohistochemistry was used to assess DC‑SIGNR protein expression in HCC and paired non‑cancerous tissue samples. DC‑SIGNR expression was lower in HCC tissues compared with adjacent non‑tumor tissue samples. The expression of DC‑SIGNR was associated with small tumor size, low Edmondson grade and high patient long term survival rates. Bioinformatics analyses were performed on several datasets to assess the potential function of DC‑SIGNR and related genes; the data revealed that DC‑SIGNR mRNA expression was lower in HCC tissues compared with non‑cancerous controls, and analyses of ten‑year survival rates indicated patients with low DC‑SIGNR expression exhibited shorter average survival times. In conclusion, decreased DC‑SIGNR expression in HCC tissues may be a relevant predictive biomarker of clinical prognosis, in addition to being a viable therapeutic target for HCC treatment.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Torre LA, Siegel RL, Ward EM and Jemal A: Global cancer incidence and mortality rates and trends-an update. Cancer Epidemiol Biomarkers Prev. 25:16–27. 2016. View Article : Google Scholar : PubMed/NCBI
3	Zuo T, Zheng R, Zeng H, Zhang S and Chen W: Analysis of liver cancer incidence and trends in China. Zhonghua Zhong Liu Za Zhi. 37:691–696. 2015.(In Chinese). PubMed/NCBI
4	Zhu Q, Qiao GL, Zeng XC, Li Y, Yan JJ, Duan R and Du ZY: Elevated expression of eukaryotic translation initiation factor 3H is associated with proliferation, invasion and tumorigenicity in human hepatocellular carcinoma. Oncotarget. 7:49888–49901. 2016.PubMed/NCBI
5	van Kooyk Y and Rabinovich GA: Protein-glycan interactions in the control of innate and adaptive immune responses. Nat Immunol. 9:593–601. 2008. View Article : Google Scholar : PubMed/NCBI
6	Chaudhary O, Kumar S, Bala M, Singh J, Hazarika A and Luthra K: Association of DC-SIGNR expression in peripheral blood mononuclear cells with DC-SIGNR genotypes in HIV-1 infection. Viral Immunol. 28:472–475. 2015. View Article : Google Scholar : PubMed/NCBI
7	Lalor PF, Lai WK, Curbishley SM, Shetty S and Adams DH: Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo. World J Gastroenterol. 12:5429–5439. 2006. View Article : Google Scholar : PubMed/NCBI
8	Engering A, van Vliet SJ, Hebeda K, Jackson DG, Prevo R, Singh SK, Geijtenbeek TB, van Krieken H and van Kooyk Y: Dynamic populations of dendritic cell-specific ICAM-3 grabbing nonintegrin-positive immature dendritic cells and liver/lymph node-specific ICAM-3 grabbing nonintegrin-positive endothelial cells in the outer zones of the paracortex of human lymph nodes. Am J Pathol. 164:1587–1595. 2004. View Article : Google Scholar : PubMed/NCBI
9	Jiang Y, Zhang C, Chen K, Chen Z, Sun Z, Zhang Z, Ding D, Ren S and Zuo Y: The clinical significance of DC-SIGN and DC-SIGNR, which are novel markers expressed in human colon cancer. PLoS One. 9:e1147482014. View Article : Google Scholar : PubMed/NCBI
10	Liu X, Zhang H, Su L, Yang P, Xin Z, Zou J, Ren S and Zuo Y: Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in lung cancer and significant correlations with brain metastasis and natural killer cells. Mol Cell Biochem. 407:151–160. 2015. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Zhang Q, Zhang M, Yuan M, Wang Z, Zhang J, Zhou X, Zhang Y, Lin F, Na H, et al: DC-SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis. Mol Cancer. 16:782017. View Article : Google Scholar : PubMed/NCBI
12	Wurmbach E, Chen YB, Khitrov G, Zhang W, Roayaie S, Schwartz M, Fiel I, Thung S, Mazzaferro V, Bruix J, et al: Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology. 45:938–947. 2007. View Article : Google Scholar : PubMed/NCBI
13	Chen X, Cheung ST, So S, Fan ST, Barry C, Higgins J, Lai KM, Ji J, Dudoit S, Ng IO, et al: Gene expression patterns in human liver cancers. Mol Biol Cell. 13:1929–1939. 2002. View Article : Google Scholar : PubMed/NCBI
14	Roessler S, Jia HL, Budhu A, Forgues M, Ye QH, Lee JS, Thorgeirsson SS, Sun Z, Tang ZY, Qin LX and Wang XW: A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients. Cancer Res. 70:10202–10212. 2010. View Article : Google Scholar : PubMed/NCBI
15	Mas VR, Maluf DG, Archer KJ, Yanek K, Kong X, Kulik L, Freise CE, Olthoff KM, Ghobrial RM, McIver P and Fisher R: Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol Med. 15:85–94. 2009. View Article : Google Scholar : PubMed/NCBI
16	Basu AK: DNA damage, mutagenesis and cancer. Int J Mol Sci. 19:9702018. View Article : Google Scholar
17	Falco M, Palma G, Rea D, De Biase D, Scala S, D'Aiuto M, Facchini G, Perdonà S, Barbieri A and Arra C: Tumour biomarkers: Homeostasis as a novel prognostic indicator. Open Biol. 6:1602542016. View Article : Google Scholar : PubMed/NCBI
18	Zhang Z, Chen K, Yan L, Yang Z, Zhu Z, Chen C, Zeng J, Wei W, Qi X, Ren S and Zuo Y: Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in non-Hodgkin lymphoma and significant correlations with lactic acid dehydrogenase and β2-microglobulin. Biochem Cell Biol. 91:214–220. 2013. View Article : Google Scholar : PubMed/NCBI
19	Na H, Liu X, Li X, Zhang X, Wang Y, Wang Z, Yuan M, Zhang Y, Ren S and Zuo Y: Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis. J Hematol Oncol. 10:282017. View Article : Google Scholar : PubMed/NCBI
20	Cox N, Pilling D and Gomer RH: DC-SIGN activation mediates the differential effects of SAP and CRP on the innate immune system and inhibits fibrosis in mice. Proc Natl Acad Sci USA. 112:8385–8390. 2015. View Article : Google Scholar : PubMed/NCBI
21	Soilleux EJ: DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): Friend or foe? Clin Sci (Lond). 104:437–446. 2003. View Article : Google Scholar : PubMed/NCBI
22	Gringhuis SI, Kaptein TM, Wevers BA, Mesman AW and Geijtenbeek TB: Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKKe- and CYLD-dependent Bcl3 activation. Nat Commun. 5:38982014. View Article : Google Scholar : PubMed/NCBI
23	Yang K, Liu X, Liu Y, Wang X, Cao L, Zhang X, Xu C, Shen W and Zhou T: DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages. Sci Rep. 7:32962017. View Article : Google Scholar : PubMed/NCBI