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Cancer Cell International
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Open Access 01-12-2023 | Hepatocellular Carcinoma | Research

Comprehensive analysis identifies CLEC1B as a potential prognostic biomarker in hepatocellular carcinoma

Authors: Qiangan Jing, Chen Yuan, Chaoting Zhou, Weidong Jin, Aiwei Wang, Yanfang Wu, Wenzhong Shang, Guibing Zhang, Xia Ke, Jing Du, Yanchun Li, Fangchun Shao

Published in: Cancer Cell International | Issue 1/2023

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Abstract

Background

C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in platelet activation, angiogenesis, and immune and inflammatory responses. However, data regarding its function and clinical prognostic value in hepatocellular carcinoma (HCC) remain scarce.

Methods

The expression of CLEC1B was explored using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RT-qPCR, western blot, and immunohistochemistry assays were employed to validate the downregulation of CLEC1B. Univariate Cox regression and survival analyses were used to evaluate the prognostic value of CLEC1B. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential association between cancer hallmarks and CLEC1B expression. The TISIDB database was applied to search for the correlation between immune cell infiltration levels and CLEC1B expression. The association between CLEC1B and immunomodulators was conducted by Spearman correlation analysis based on the Sangerbox platform. Annexin V-FITC/PI apoptosis kit was used for the detection of cell apoptosis.

Results

The expression of CLEC1B was low in various tumors and exhibited a promising clinical prognostic value for HCC patients. The expression level of CLEC1B was tightly associated with the infiltration of various immune cells in the HCC tumor microenvironment (TME) and positively correlated with a bulk of immunomodulators. In addition, CLEC1B and its related genes or interacting proteins are implicated in multiple immune-related processes and signaling pathways. Moreover, overexpression of CLEC1B significantly influenced the treatment effects of sorafenib on HCC cells.

Conclusions

Our results reveal that CLEC1B could serve as a potential prognostic biomarker and may be a novel immunoregulator for HCC. However, its function in immune regulation should be further explored.
Appendix
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Literature
1.
2.
3.
Yang JD, Hainaut P, Gores GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management[J]. Nat Reviews Gastroenterol Hepatol. 2019;16(10):589–604.CrossRef
4.
Llovet JM, Kelley RK, Villanueva A et al. Hepatocellular carcinoma[J]. Nat Reviews Disease Primers, 2021, 7(1).
5.
Petrowsky H, Fritsch R, Guckenberger M, et al. Modern therapeutic approaches for the treatment of malignant liver tumours[J]. Nat Reviews Gastroenterol Hepatol. 2020;17(12):755–72.CrossRef
6.
Rebouissou S, Nault J-C. Advances in molecular classification and precision oncology in hepatocellular carcinoma[J]. J Hepatol. 2020;72(2):215–29.CrossRefPubMed
7.
Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial[J]. Lancet. 2016;387(10031):1909–20.PubMedCentralCrossRefPubMed
8.
Giraldo NA, Becht E, Vano Y, et al. Tumor-infiltrating and peripheral blood T-cell immunophenotypes predict early relapse in localized clear cell renal cell carcinoma[J]. Clin Cancer Res. 2017;23(15):4416–28.CrossRefPubMed
9.
Salmon H, Remark R, Gnjatic S, et al. Host tissue determinants of tumour immunity[J]. Nat Rev Cancer. 2019;19(4):215–27.PubMedCentralPubMed
10.
Zhang G, Lv X, Yang Q, et al. Identification of HM13 as a prognostic indicator and a predictive biomarker for immunotherapy in hepatocellular carcinoma[J]. BMC Cancer. 2022;22(1):888.PubMedCentralCrossRefPubMed
11.
Pitt JM, Marabelle A, Eggermont A, et al. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy[J]. Ann Oncol. 2016;27(8):1482–92.CrossRefPubMed
12.
Mi H, Ho WJ, Yarchoan M, et al. Multi-scale spatial analysis of the tumor microenvironment reveals features of cabozantinib and nivolumab efficacy in hepatocellular carcinoma[J]. Front Immunol. 2022;13:892250.PubMedCentralCrossRefPubMed
13.
Zhu AX, Abbas AR, De Galarreta MR, et al. Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma[J]. Nat Med. 2022;28(8):1599–611.CrossRefPubMed
14.
Ott PA, Hodi FS, Kaufman HL et al. Combination immunotherapy: a road map[J]. J Immunother Cancer, 2017, 5.
15.
Finn RS, Ryoo B-Y, Merle P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in keynote-240: a randomized, double-blind, phase III trial[J]. J Clin Oncol. 2020;38(3):193–.CrossRefPubMed
16.
Huysamen C, Brown GD. The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors[J]. FEMS Microbiol Lett. 2009;290(2):121–8.CrossRefPubMed
17.
18.
Suzuki-Inoue K, Kato Y, Inoue O, et al. Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells[J]. J Biol Chem. 2007;282(36):25993–6001.CrossRefPubMed
19.
Critelli R, Milosa F, Faillaci F, et al. Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study[J]. Cell Death & Disease; 2017. p. 8.
20.
Zhang GH, Su LS, Lv XP et al. A novel tumor doubling time-related immune gene signature for prognosis prediction in hepatocellular carcinoma[J]. Cancer Cell Int, 2021, 21(1).
21.
Hu K, Wang ZM, Li JN, et al. CLEC1B expression and PD-L1 expression predict clinical outcome in hepatocellular carcinoma with tumor hemorrhage[J]. Translational Oncol. 2018;11(2):552–8.CrossRef
22.
Rayes J, Lax S, Wichaiyo S et al. The podoplanin-CLEC-2 axis inhibits inflammation in sepsis[J]. Nat Commun, 2017, 8.
23.
Sun D, Wang J, Han Y, et al. TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment[J]. Nucleic Acids Res. 2021;49(D1):D1420–30.CrossRefPubMed
24.
Ru B, Wong CN, Tong Y, et al. TISIDB: an integrated repository portal for tumor-immune system interactions[J]. Bioinformatics. 2019;35(20):4200–2.CrossRefPubMed
25.
Bindea G, Mlecnik B, Tosolini M, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer[J]. Immunity. 2013;39(4):782–95.CrossRefPubMed
26.
Haenzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-Seq data[J]. BMC Bioinformatics, 2013, 14.
27.
Jing Q, Yao H, Li H, et al. A novel RNA modification prognostic signature for predicting the characteristics of the tumor microenvironment in gastric cancer[J]. Front Oncol. 2023;13:905139.PubMedCentralCrossRefPubMed
28.
Wang X, Xu B, Du J et al. Characterization of pyruvate metabolism and citric acid cycle patterns predicts response to immunotherapeutic and ferroptosis in gastric cancer[J]. Cancer Cell Int, 2022, 22(1).
29.
Hu J, Yu A, Othmane B, et al. Siglec15 shapes a non-inflamed tumor microenvironment and predicts the molecular subtype in bladder cancer[J]. Theranostics. 2021;11(7):3089–108.PubMedCentralCrossRefPubMed
30.
Shen W, Song Z, Zhong X et al. Sangerbox: a comprehensive, interaction-friendly clinical bioinformatics analysis platform[J]. iMeta, 2022, 1(3).
31.
Liberzon A, Birger C, Thorvaldsdóttir H, et al. The molecular signatures database (MSigDB) hallmark gene set collection[J]. Cell Syst. 2015;1(6):417–25.PubMedCentralCrossRefPubMed
32.
Yu G, Wang L-G, Han Y, et al. clusterProfiler: an R package for comparing biological themes among gene clusters[J]. Omics-a J Integr Biology. 2012;16(5):284–7.CrossRef
33.
Bindea G, Mlecnik B, Hackl H, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks[J]. Bioinformatics. 2009;25(8):1091–3.PubMedCentralCrossRefPubMed
34.
Hu W, Zhou C, Jing Q et al. FTH promotes the proliferation and renders the HCC cells specifically resist to ferroptosis by maintaining iron homeostasis[J]. Cancer Cell Int, 2021, 21(1).
35.
Li Y, Xu B, Ren X, et al. Inhibition of CISD2 promotes ferroptosis through ferritinophagy-mediated ferritin turnover and regulation of p62-Keap1-NRF2 pathway[J]. Volume 27. Cellular & Molecular Biology Letters; 2022. 1.
36.
Du J, Wang TT, Li YC, et al. DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin[J]. Free Radic Biol Med. 2019;131:356–69.CrossRefPubMed
37.
Sounni NE, Noel A. Targeting the tumor microenvironment for cancer therapy[J]. Clin Chem. 2013;59(1):85–93.CrossRefPubMed
38.
Fridman WH, Pages F, Sautes-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome[J]. Nat Rev Cancer. 2012;12(4):298–306.CrossRefPubMed
39.
Bejarano L, Jordāo MJC, Joyce JA. Therapeutic targeting of the tumor microenvironment[J]. Cancer Discov. 2021;11(4):933–59.CrossRefPubMed
40.
Yoshihara K, Shahmoradgoli M, Martínez E, et al. Inferring tumour purity and stromal and immune cell admixture from expression data[J]. Nat Commun. 2013;4:2612.CrossRefPubMed
41.
Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis[J]. Trends Cell Biol. 2019;29(3):212–26.CrossRefPubMed
42.
Mittal V. Epithelial Mesenchymal Transition in Tumor Metastasis, Abbas A K, Aster J C, editor, Annual Review of Pathology: Mechanisms of Disease, Vol 13, 2018: 395–412.
43.
44.
45.
Suzuki-Inoue K. The novel platelet activation receptor CLEC-2[J]. Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan. 2007;127:17–8.
46.
Hess PR, Rawnsley DR, Jakus Z, et al. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life[J]. J Clin Invest. 2014;124(1):273–84.CrossRefPubMed
47.
Lowe KL, Navarro-Nunez L, Watson SP. Platelet CLEC-2 and podoplanin in cancer metastasis[J]. Thromb Res. 2012;129:30–S37.CrossRef
48.
Hu K, Wang ZM, Li JN, et al. CLEC1B expression and PD-L1 expression predict clinical outcome in hepatocellular carcinoma with tumor hemorrhage[J]. Transl Oncol. 2018;11(2):552–8.PubMedCentralCrossRefPubMed
49.
50.
Tu Z, Ouyang Q, Long X et al. Protein disulfide-isomerase A3 is a robust prognostic biomarker for cancers and predicts the immunotherapy response effectively[J]. Front Immunol, 2022, 13.
51.
Li H, Xu B, Du J, et al. Autophagy-related prognostic signature characterizes tumor microenvironment and predicts response to ferroptosis in gastric cancer[J]. Front Oncol. 2022;12:959337–7.PubMedCentralCrossRefPubMed
52.
Wculek SK, Cueto FJ, Mujal AM, et al. Dendritic cells in cancer immunology and immunotherapy[J]. Nat Rev Immunol. 2020;20(1):7–24.CrossRefPubMed
53.
De Winde CM, Matthews AL, Van Deventer S et al. C-type lectin-like receptor 2 (CLEC-2)-dependent dendritic cell migration is controlled by tetraspanin CD37[J]. J Cell Sci, 2018, 131(19).
54.
55.
56.
Van Der Leun AM, Thommen DS, Schumacher TN. CD8(+) T cell states in human cancer: insights from single-cell analysis[J]. Nat Rev Cancer. 2020;20(4):218–32.PubMedCentralCrossRefPubMed
57.
Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy[J]. Nat Rev Immunol. 2017;17(9):559–72.PubMedCentralCrossRefPubMed
58.
Liang X, Song F, Fang W, et al. CLEC1B is a promising prognostic biomarker and correlated with immune infiltration in hepatocellular carcinoma[J]. Int J Gen Med. 2022;15:5661–72.PubMedCentralCrossRefPubMed
59.
Cheng Q, Duan WW, He SQ et al. Multi-omics data integration analysis of an immune-related gene signature in LGG patients with epilepsy[J]. Front Cell Dev Biology, 2021, 9.
60.
May F, Hagedorn I, Pleines I, et al. CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis[J]. Blood. 2009;114(16):3464–72.CrossRefPubMed
61.
Wang L, Yin J, Wang X, et al. C-type lectin-like receptor 2 suppresses AKT signaling and invasive activities of gastric cancer cells by blocking expression of phosphoinositide 3-kinase subunits[J]. Gastroenterology. 2016;150(5):1183–1195e16.CrossRefPubMed
62.
Suzuki-Inoue K, Fuller GLJ, Garcia A, et al. A novel syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2[J]. Blood. 2006;107(2):542–9.CrossRefPubMed
63.
Moroi AJ, Watson SP. Akt and mitogen-activated protein kinase enhance C-type lectin-like receptor2-mediated platelet activation by inhibition of glycogen synthase kinase 3 alpha/beta[J]. J Thromb Haemost. 2015;13(6):1139–50.PubMedCentralCrossRefPubMed
64.
Moroi AJ, Watson SP. Impact of the PI3-kinase/Akt pathway on ITAM and hemITAM receptors: Haemostasis, platelet activation and antithrombotic therapy[J]. Biochem Pharmacol. 2015;94(3):186–94.CrossRefPubMed
Metadata
Title
Comprehensive analysis identifies CLEC1B as a potential prognostic biomarker in hepatocellular carcinoma
Authors
Qiangan Jing
Chen Yuan
Chaoting Zhou
Weidong Jin
Aiwei Wang
Yanfang Wu
Wenzhong Shang
Guibing Zhang
Xia Ke
Jing Du
Yanchun Li
Fangchun Shao
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2023
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-023-02939-1

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