Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity.
Apelin/APJ axis
Apoptosis
Hepatocellular carcinoma
Real-Time PCR
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
04
06
2020
accepted:
04
11
2020
pubmed:
18
11
2020
medline:
23
11
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
Apelin, a peptide of 77 amino acids, and its endogenous ligand, angiotensin-like-receptor 1 (APJ), play a key role in the development of tumors by enhancing angiogenesis, metastasis, cell proliferation, development of cancer stem cells and drug resistance and inhibiting apoptosis of cancer cells. However, little is known about Apelin/APJ system involvement in hepatocellular carcinoma (HCC). The aim of this study was to evaluate Apelin and APJ expression in liver specimens, obtained from subjects with HCV-positive HCC who underwent liver transplantation, according to liver disease severity (liver recipients, LR, n = 14, age 59.4 ± 1.8) and in donors (liver donors, LD, n = 14, age 62.1 ± 17.3). Apelin/APJ axis, apoptotic and inflammatory markers were evaluated by Real-Time PCR analysis. The Apelin/APJ system expression resulted significantly higher in LR in comparison with LD (p < 0.05), in particular in those with more severe liver disease. The apoptotic (Bcl-2, BAX, NOTCH-1, Casp-3) and inflammatory (IL-6, TNF-α) markers were increased as a function of disease severity (p < 0.05). Multiple significant positive correlations were found between Apelin/APJ axis and the other markers. Although further investigations are needed to better understand the role of Apelin/APJ axis in HCC, our result indicated a potential role of this axis in its development and progression as well as in recognizing novel therapeutic targets opening a new avenue for treatment.
Identifiants
pubmed: 33201338
doi: 10.1007/s10238-020-00672-x
pii: 10.1007/s10238-020-00672-x
doi:
Substances chimiques
APLNR protein, human
0
Apelin
0
Apelin Receptors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
269-275Références
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–404.
pubmed: 30207593
Gomaa AI, Khan SA, Toledano MB, Waked I, Taylor-Robinson SD. Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol. 2008;14:4300–8.
pubmed: 18666317
pmcid: 2731180
Zhu AX, Duda DG, Sahani DV, Jain RK. HCC and angiogenesis: possible targets and future directions. Nat Rev Clin Oncol. 2011;8:292–301.
pubmed: 21386818
pmcid: 3266719
Muto J, Shirabe K, Sugimachi K, Maehara Y. Review of angiogenesis in hepatocellular carcinoma. Hepatolo Res Off J Japan Soc Hepato. 2015;45:1–9.
Matsui O, Kobayashi S, Sanada J, et al. Hepatocelluar nodules in liver cirrhosis: hemodynamic evaluation (angiography-assisted CT) with special reference to multi-step hepatocarcinogenesis. Abdom Imaging. 2011;36:264–72.
pubmed: 21267562
pmcid: 3102849
Hanish SI, Knechtle SJ. Liver transplantation for the treatment of hepatocellular carcinoma. Oncology. 2011;25(8):25752.
Bhardwaj N, Perera MT, Silva MA. Current treatment approachesto HCC with a special consideration to transplantation. J Transpl. 2016;2016:7926264.
Toniutto P, Zanetto A, Ferrarese A, Burra P. Current challenges and future directions for liver transplantation. Liver Int. 2017;37:317–27.
pubmed: 27634369
Freeman RB, Edwards EB, Harper AM. Waiting list removal rates among patients with chronic and malignant liver diseases. Am J Transpl. 2006;6:1416–21.
Wiesner RH, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91–6.
pubmed: 12512033
Wiesner RH, McDiarmid SV, Kamath PS, et al. MELD and PELD: application of survival models to liver allocation. Liver Transpl. 2001;7:567–80.
pubmed: 11460223
Huo TI, Huang YH, Su CW, et al. Validation of the HCC-MELD for dropout probability in patients with small hepatocellular carcinoma undergoing locoregional therapy. Clin Transpl. 2008;22:469–75.
Huynh H, Ong RW, Li PY, et al. Targeting receptor tyrosine kinase pathways in hepatocellular carcinoma. Anticancer Agents Med Chem. 2011;11:560–75.
pubmed: 21554207
Zhou Q, Lui VW, Yeo W. Targeting the PI3K/Akt/mTOR pathway in hepatocellular carcinoma. Future Oncol. 2011;7:1149–67.
pubmed: 21992728
Cavard C, Colnot S, Audard V, et al. Wnt/beta-catenin pathway in hepatocellular carcinoma pathogenesis and liver physiology. Future Oncol. 2008;4:647–60.
pubmed: 18922122
Chen YJ, Wu H, Shen XZ. The ubiquitin-proteasome system and its potential application in hepatocellular carcinoma therapy. Cancer Lett. 2016;379:245–52.
pubmed: 26193663
Morse MA, Sun W, Kim R, et al. The role of angiogenesis in hepatocellular carcinoma. Clin Cancer Res. 2019;25:912–20.
pubmed: 30274981
Zhu AX. Systemic treatment of hepatocellular carcinoma: dawn of a new era? Ann Surg Oncol. 2010;17:1247–56.
pubmed: 20405329
Eyries M, Siegfried G, Ciumas M, et al. Hypoxia-induced Apelin expression regulates endothelial cell proliferation and regenerative angiogenesis. Circ Res. 2008;103:432–40.
pubmed: 18617693
Kidoya H, Ueno M, Yamada Y, et al. Spatial and temporal role of the Apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis. EMBO J. 2008;27:522–34.
pubmed: 18200044
pmcid: 2241654
Berta J, Kenessey I, Dobos J, et al. Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol. 2010;5:1120–9.
pubmed: 20581707
Heo K, Kim YH, Sung HJ, et al. Hypoxia-induced up-regulation of Apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncol. 2012;48:500–6.
pubmed: 22285858
Wang Z, Greeley GH Jr, Qiu S. Immunohistochemical localization of Apelin in human normal breast and breast carcinoma. J Mol Histol. 2008;39:121–4.
pubmed: 17823846
Muto J, Shirabe K, Yoshizumi T, et al. The Apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. Anticancer Res. 2014;34:5313–20.
pubmed: 25275024
Hashimoto T, Kihara M, Ishida J, et al. Apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2006;26:1267–72.
pubmed: 16556853
Masoumi J, Jafarzadeh A, Khorramdelazad H, Abbasloui M, Abdolalizadeh J, Jamali N. Role of Apelin/APJ axis in cancer development and progression. Adv Med Sci. 2020;65:202–13.
pubmed: 32087570
Cui RR, Mao DA, Yi L, et al. Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways. Amino Acids. 2010;39:1193–200.
pubmed: 20495838
Cabiati M, Gaggini M, Cesare MM, et al. Osteopontin in hepatocellular carcinoma: a possible biomarker for diagnosis and follow-up. Cytokine. 2017;99:59–65.
pubmed: 28711012
Cabiati M, Gaggini M, De Simone P, et al. Assessment of RANKL/RANK/osteoprotegerin system expression in patients with hepatocellular carcinoma. Minerva Endocrinologica. “Letter to the Editor” 2020 in press.
Bustin SA, Benes V, Garson JA, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55:611–22.
pubmed: 19246619
Farid RM, Abu-Zeid RM, El-Tawil A. Emerging role of adipokine apelin in hepatic remodelling and initiation of carcinogensis in chronic hepatitis C patients. Int J Clin Exp Pathol. 2014;7:2707.
pubmed: 24966992
pmcid: 4069886
Lacquaniti A, Altavilla G, Picone A, et al. Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation. Clin Exp Med. 2015;15:97–105.
pubmed: 24469934
Wang C, Wen J, Zhou Y, et al. Apelin induces vascular smooth muscle cells migration via a PI3K/Akt/FoxO3a/MMP-2 pathway. Int J Biochem Cell Biol. 2015;69:173–82.
pubmed: 26494002
Liu QF, Yu HW, You L, Liu M-X, Li K-Y, Tao G-Z. Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1. Biochem Biophys Res Commun. 2013;439:235–40.
pubmed: 23973488
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495–516.
pubmed: 17562483
pmcid: 2117903
Karimabad MN, Mahmoodi M, Jafarzadeh A, et al. The novel Indole-3-formaldehyde (2-AITFEI-3-F) is involved in processes of apoptosis induction? Life Sci. 2017;181:31–44.
pubmed: 28549559
Engel T, Henshall DC. Apoptosis, Bcl-2 family proteins and caspases: the ABCs of seizure-damage and epileptogenesis? Int J Physiol Pathophysiol Pharmacol. 2009;1:97.
pubmed: 21383882
pmcid: 3047241
Kelly PN, Strasser A. The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ. 2011;18:1414.
pubmed: 21415859
pmcid: 3149740
Mackey TJ, Borkowski A, Amin P, Jacobs SC, Kyprianou N. bcl-2/BAX ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer. Urology. 1998;52:1085–90.
pubmed: 9836559
Raffo AJ, Perlman H, Chen MW, Day ML, Streitman JS, Buttyan R. Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res. 1995;55:4438–45.
pubmed: 7671257
Cao C, Wang C. Clinical significance of serum miR-768–3p in HBV-related hepatocellular carcinoma and its potential mechanism. Clin Exp Med. 2020. https://doi.org/10.1007/s10238-020-00646-z .
doi: 10.1007/s10238-020-00646-z
pubmed: 32712720
Qu L, Cai X, Xu J, et al. Six long noncoding RNAs as potentially biomarkers involved in competitive endogenous RNA of hepatocellular carcinoma. Clin Exp Med. 2020;20(3):437–47.
pubmed: 32514710
Feder S, Haberl EM, Spirk M, Weiss TS, Wiest R, Buechler C. Pentraxin-3 is not related to disease severity in cirrhosis and hepatocellular carcinoma patients. Clin Exp Med. 2020;20(2):289–97.
pubmed: 32078718
pmcid: 7181432
Wu L, Chen P, Ying J, et al. MAT2B mediates invasion and metastasis by regulating EGFR signaling pathway in hepatocellular carcinoma. Clin Exp Med. 2019;19(4):535–46.
pubmed: 31493275