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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

General Research Article

The Diagnostic and Therapeutic Value of NCAPG as a Proposed Biomarker Candidate in Acute Liver Failure

Author(s): Lu Zhang, Tao Ma, Yang Yan, Yu-Yan Chen, Xin-Hua Zhu* and Hao-Zhen Ren*

Volume 26, Issue 15, 2023

Published on: 11 May, 2023

Page: [2738 - 2748] Pages: 11

DOI: 10.2174/1386207326666230416165707

Price: $65

Abstract

Background: Acute Liver Failure (ALF) is a difficult problem to solve in clinical practice. The presence of non-SMC condensin I complex subunit G (NCAPG) has previously been linked to vascular invasion of digestive system tumors, foreshadowing poor prognosis. Its role in ALF biology, however, remains unknown. This article explores the role of NCAPG as a potential biomarker candidate for the accurate diagnosis and targeted treatment of ALF.

Methods: The study included transcription data (GSE14668, GSE38941, GSE62029, GSE96851, and GSE120652) of ALF, normal tissues, and clinical samples, where NCAPG was selected as the differential gene by the “DESeq2” R package to analyze the immune cell functions and signal pathways. Furthermore, RT-qPCR and Western blot analyses were used to confirm the RNA and protein levels of NCAPG in ALF cell models, respectively.

Results: Bioinformatics analysis revealed that NACPG was up-regulated in ALF tissues, and the functional signaling pathway was primarily associated with immune infiltration. Based on the results of clinical samples, we suggest that NCAPG was overexpressed in ALF tissues. We also found that the expression of NCAPG increased with the degree of liver injury in vitro. Enrichment analysis suggested that NCAPG influenced ALF as a PI3K/AKT pathway activator.

Conclusion: Our study suggests that NCAPG is a preliminary tool for the diagnosis of ALF. It can affect ALF via the PI3K/AKT pathway and is a potential therapeutic target to improve prognosis.

Graphical Abstract

[1]
Bernal, W.; McPhail, M.J. Acute liver failure. J. Hepatol., 2021, 74(6), 1489-1490.
[http://dx.doi.org/10.1016/j.jhep.2021.01.037] [PMID: 33845974]
[2]
Thanapirom, K.; Teerasarntipan, T.; Treeprasertsuk, S.; Choudhury, A.; Sahu, M.K.; Maiwall, R.; Pamecha, V.; Moreau, R.; Al Mahtab, M.; Chawla, Y.K.; Devarbhavi, H.; Yu, C.; Ning, Q.; Amarapurkar, D.; Eapen, C.E.; Hamid, S.S.; Butt, A.S.; Kim, D.J.; Lee, G.H.; Sood, A.; Lesmana, L.A.; Abbas, Z.; Shiha, G.; Payawal, D.A.; Yuen, M.F.; Chan, A.; Lau, G.; Jia, J.; Rahman, S.; Sharma, B.C.; Yokosuka, O.; Sarin, S.K.; Sarin, S.K.; Choudhury, A.; Sharma, M.K.; Maiwall, R.; Mahtab, M.A.; Rahman, S.; Saigal, S.; Saraf, N.; Soin, A.S.; Devarbhavi, H.; Kim, D.J.; Dhiman, R.K.; Duseja, A.; Taneja, S.; Eapen, C.E.; Goel, A.; Ning, Q.; Chen, T.; Ma, K.; Duan, Z.; Yu, C.; Treeprasertsuk, S.; Hamid, S.S.; Butt, A.S.; Jafri, W.; Shukla, A.; Saraswat, V.; Tan, S.S.; Sood, A.; Midha, V.; Goyal, O.; Ghazinyan, H.; Arora, A.; Hu, J.; Sahu, M.; Rao, P.N.; Lee, G.H.; Lim, S.G.; Lesmana, L.A.; Lesmana, C.R.; Shah, S.; Mohan Prasad, V.G.; Payawal, D.A.; Abbas, Z.; Kadir Dokmeci, A.; Sollano, J.D.; Carpio, G.; Shresta, A.; Lau, G.K.; Fazal Karim, M.; Shiha, G.; Gani, R.; Kalista, K.F.F.; Yuen, M-F.; Alam, S.; Khanna, R.; Sood, V.; Lal, B.B.; Pamecha, V.; Jindal, A.; Rajan, V.; Arora, V.; Yokosuka, O.; Niriella, M.A.; Li, H.; Qi, X.; Tanaka, A.; Mochida, S.; Chaudhuri, D.R.; Gane, E.; Win, K.M.; Chen, W.T.; Rela, M.; Kapoor, D.; Rastogi, A.; Kale, P.; Rastogi, A.; Sharma, C.B.; Bajpai, M.; Singh, V.; Premkumar, M.; Sudhir, S.; Olithselvan, A.; Philips, C.A.; Srivastava, A.; Yachha, S.K.; Wani, Z.A.; Thapa, B.R.; Saraya, A. Shalimar; Kumar, A.; Wadhawan, M.; Gupta, S.; Madan, K.; Sakhuja, P.; Vij, V.; Sharma, B.C.; Garg, H.; Garg, V.; Kalal, C.; Anand, L.; Vyas, T.; Mathur, R.P.; Kumar, G.; Jain, P.; Pasupuleti, S.S.R.; Chawla, Y.K.; Chowdhury, A.; Alam, S.; Song, D.S.; Yang, J.M. Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure. Hepatol. Int., 2022, 16(1), 171-182.
[http://dx.doi.org/10.1007/s12072-021-10266-8] [PMID: 34822057]
[3]
Anastasiou, O.E.; Widera, M.; Westhaus, S.; Timmer, L.; Korth, J.; Gerken, G.; Canbay, A.; Todt, D.; Steinmann, E.; Schwarz, T.; Timm, J.; Verheyen, J.; Ciesek, S. Clinical outcome and viral genome variability of hepatitis B virus-induced acute liver failure. Hepatology, 2019, 69(3), 993-1003.
[http://dx.doi.org/10.1002/hep.30279] [PMID: 30229977]
[4]
Björnsson, H.K.; Björnsson, E.S. Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management. Eur. J. Intern. Med., 2022, 97, 26-31.
[http://dx.doi.org/10.1016/j.ejim.2021.10.035] [PMID: 34772600]
[5]
Wong, F.; Piano, S.; Singh, V.; Bartoletti, M.; Maiwall, R.; Alessandria, C.; Fernandez, J.; Soares, E.C.; Kim, D.J.; Kim, S.E.; Marino, M.; Vorobioff, J.; Barea, R.C.R.; Merli, M.; Elkrief, L.; Vargas, V.; Krag, A.; Singh, S.P.; Lesmana, L.A.; Toledo, C.; Marciano, S.; Verhelst, X.; Intagliata, N.; Rabinowich, L.; Colombato, L.; Kim, S.G.; Gerbes, A.; Durand, F.; Roblero, J.P.; Bruns, T.; Yoon, E.L.; Girala, M.; Pyrsopoulos, N.T.; Kim, T.H.; Yim, S.Y.; Juanola, A.; Gadano, A.; Angeli, P.; Bhamidimarri, K.; Boyer, T.D.; Brodersen, C.; Campion, D.; Caraceni, P.; de Man, R.A.; Fassio, E.; Fialla, A.D.; Gambino, C.; Gautam, V.; Gines, P.; Hwang, J.S.; Kim, H.S.; Kim, J.H.; Kumar, P.; Lattanz, B.; Lee, T.H.; Rinaldi Lesmana, C.A.; Maevskaya, M.; Nath, P.; Navarro, G.; Park, J-W.; Pinero, G.; Restellini, S.; Romero, G. Sevá -Pereira, T.; Simón-Talero, M.; Song, D.S.; Suk, K.T.; Van Vlierberghe, H.; Zaccherini, G. International Club of Ascites Global Study Group. Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure. J. Hepatol., 2021, 74(2), 330-339.
[http://dx.doi.org/10.1016/j.jhep.2020.07.046] [PMID: 32781201]
[6]
Rahim, M.N.; Miquel, R.; Heneghan, M.A. Approach to the patient with acute severe autoimmune hepatitis. JHEP Reports, 2020, 2(6), 100149.
[http://dx.doi.org/10.1016/j.jhepr.2020.100149] [PMID: 32995712]
[7]
Gustot, T.; Fernandez, J.; Garcia, E.; Morando, F.; Caraceni, P.; Alessandria, C.; Laleman, W.; Trebicka, J.; Elkrief, L.; Hopf, C.; Solís-Munoz, P.; Saliba, F.; Zeuzem, S.; Albillos, A.; Benten, D.; Montero-Alvarez, J.L.; Chivas, M.T.; Concepción, M.; Córdoba, J.; McCormick, A.; Stauber, R.; Vogel, W.; de Gottardi, A.; Welzel, T.M.; Domenicali, M.; Risso, A.; Wendon, J.; Deulofeu, C.; Angeli, P.; Durand, F.; Pavesi, M.; Gerbes, A.; Jalan, R.; Moreau, R.; Ginés, P.; Bernardi, M.; Arroyo, V.; Aguilar-Melero, P.; Bañares, R.; Bocci, M.; Catalina, M.V.; Chin, J.L.; Coenraad, M.J.; Coilly, A.; Dorn, L.; Gatta, A.; Gerber, L.; Grøenbæk, H.; Graupera, I.; Guevara, M.; Hausen, A.; Karlsen, S.; Lohse, A.W.; Maggioli, C.; Markwardt, D.; Martinez, J.; Marzano, A.; de la Mata García, M.; Mesonero, F.; Mookerjee, R.P.; Moreno, C.; Morrell, B.; Mortensen, C.; Nevens, F.; Peck-Radosavljevic, M.; Rizzetto, M.; Romano, A.; Samuel, D.; Sauerbruch, T.; Simon-Talero, M.; Solà, E.; Soriano, G.; Sperl, J.; Spindelboeck, W.; Steib, C.; Valla, D.; Verbeke, L.; Van Vlierberghe, H.; Wege, H.; Willars, C.; Baenas, M.Y.; Zaccherini, G. Clinical Course of acute on chronic liver failure syndrome and effects on prognosis. Hepatology, 2015, 62(1), 243-252.
[http://dx.doi.org/10.1002/hep.27849] [PMID: 25877702]
[8]
Karvellas, C.J.; Speiser, J.L.; Tremblay, M.; Lee, W.M.; Rose, C.F. US Acute Liver Failure Study Group. Elevated FABP1 serum levels are associated with poorer survival in acetaminophen-induced acute liver failure. Hepatology, 2017, 65(3), 938-949.
[http://dx.doi.org/10.1002/hep.28945] [PMID: 27859489]
[9]
Wu, D.; Zhang, S.; Xie, Z.; Chen, E.; Rao, Q.; Liu, X.; Huang, K.; Yang, J.; Xiao, L.; Ji, F.; Jiang, Z.; Zhao, Y.; Ouyang, X.; Zhu, D.; Dai, X.; Hou, Z.; Liu, B.; Deng, B.; Zhou, N.; Gao, H.; Sun, Z.; Li, L. Plasminogen as a prognostic biomarker for HBV-related acute-on-chronic liver failure. J. Clin. Invest., 2020, 130(4), 2069-2080.
[http://dx.doi.org/10.1172/JCI130197] [PMID: 32175919]
[10]
Tavabie, O.D.; Karvellas, C.J.; Salehi, S.; Speiser, J.L.; Rose, C.F.; Menon, K.; Prachalias, A.; Heneghan, M.A.; Agarwal, K.; Lee, W.M.; McPhail, M.J.W.; Aluvihare, V.R.; Lee, W.M.; Larson, A.M.; Liou, I.; Fix, O.; Schilsky, M.; McCashland, T.; Hay, J.E.; Murray, N.; Shaikh, A.O.S.; Blei, A.; Ganger, D.; Zaman, A.; Han, S.H.B.; Fontana, R.; McGuire, B.; Chung, R.T.; Smith, A.; Brown, R.; Crippin, J.; Harrison, E.; Reuben, A.; Munoz, S.; Reddy, R.; Stravitz, R.T.; Rossaro, L.; Satyanarayana, R.; Hassanein, T.; Karvellas, C.J.; Olson, J.; Subramanian, R.; Hanje, J.; Hameed, B.; Lalani, E.; Pezzia, C.; Sanders, C.; Attar, N.; Hynan, L.S.; Durkalski, V.; Zhao, W.; Speiser, J.; Dillon, C.; Battenhouse, H.; Gottfried, M. United States Acute Liver Failure Study Group. A novel microRNA-based prognostic model outperforms standard prognostic models in patients with acetaminophen-induced acute liver failure. J. Hepatol., 2021, 75(2), 424-434.
[http://dx.doi.org/10.1016/j.jhep.2021.03.013] [PMID: 33857547]
[11]
Eberlein, A.; Takasuga, A.; Setoguchi, K.; Pfuhl, R.; Flisikowski, K.; Fries, R.; Klopp, N.; Fürbass, R.; Weikard, R.; Kühn, C. Dissection of genetic factors modulating fetal growth in cattle indicates a substantial role of the non-SMC condensin I complex, subunit G (NCAPG) gene. Genetics, 2009, 183(3), 951-964.
[http://dx.doi.org/10.1534/genetics.109.106476] [PMID: 19720859]
[12]
Liu, J.; Feng, M.; Li, S.; Nie, S.; Wang, H.; Wu, S.; Qiu, J.; Zhang, J.; Cheng, W. Identification of molecular markers associated with the progression and prognosis of endometrial cancer: a bioinformatic study. Cancer Cell Int., 2020, 20(1), 59.
[http://dx.doi.org/10.1186/s12935-020-1140-3] [PMID: 32099532]
[13]
Ferrer, C.M.; Lu, T.Y.; Bacigalupa, Z.A.; Katsetos, C.D.; Sinclair, D.A.; Reginato, M.J. O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway. Oncogene, 2017, 36(4), 559-569.
[http://dx.doi.org/10.1038/onc.2016.228] [PMID: 27345396]
[14]
Song, B.; Du, J.; Song, D.; Ren, J.; Feng, Y. Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer. Biol. Res., 2018, 51(1), 44.
[http://dx.doi.org/10.1186/s40659-018-0192-5] [PMID: 30390708]
[15]
Liu, C.; Yan, Y.; Di, F.; Li, W.; Yin, X.; Dong, L. Inhibition of NCAPG expression inactivates the Wnt/βcatenin signal to suppresses endometrial cancer cell growth in vitro. Environ. Toxicol., 2021, 36(12), 2512-2520.
[http://dx.doi.org/10.1002/tox.23364] [PMID: 34480403]
[16]
Gong, C.; Ai, J.; Fan, Y.; Gao, J.; Liu, W.; Feng, Q.; Liao, W.; Wu, L. NCAPG promotes the proliferation of hepatocellular carcinoma through PI3K/AKT signaling. OncoTargets Ther., 2019, 12, 8537-8552.
[http://dx.doi.org/10.2147/OTT.S217916] [PMID: 31802891]
[17]
Yu, G.; Wang, L.G.; Han, Y.; He, Q.Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5), 284-287.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[18]
Han, Y.; Yu, G.; Sarioglu, H.; Caballero-Martinez, A.; Schlott, F.; Ueffing, M.; Haase, H.; Peschel, C.; Krackhardt, A.M. Proteomic investigation of the interactome of FMNL1 in hematopoietic cells unveils a role in calcium-dependent membrane plasticity. J. Proteomics, 2013, 78, 72-82.
[http://dx.doi.org/10.1016/j.jprot.2012.11.015] [PMID: 23182705]
[19]
Krenkel, O.; Mossanen, J.C.; Tacke, F. Immune mechanisms in acetaminophen-induced acute liver failure. Hepatobiliary Surg. Nutr., 2014, 3(6), 331-343.
[PMID: 25568858]
[20]
Yang, T.; Wang, H.; Wang, X.; Li, J.; Jiang, L. The dual role of innate immune response in acetaminophen-induced liver injury. Biology, 2022, 11(7), 1057.
[http://dx.doi.org/10.3390/biology11071057] [PMID: 36101435]
[21]
Wang, Y.; Yang, F.; Jiao, F.Z.; Chen, Q.; Zhang, W.B.; Wang, L.W.; Gong, Z.J. Modulations of histone deacetylase 2 offer a protective effect through the mitochondrial apoptosis pathway in acute liver failure. Oxid. Med. Cell. Longev., 2019, 2019, 8173016.
[http://dx.doi.org/10.1155/2019/8173016] [PMID: 31183000]
[22]
Yu, Z.; Li, J.; Ren, Z.; Sun, R.; Zhou, Y.; Zhang, Q.; Wang, Q.; Cui, G.; Li, J.; Li, A.; Duan, Z.; Xu, Y.; Wang, Z.; Yin, P.; Piao, H.; Lv, J.; Liu, X.; Wang, Y.; Fang, M.; Zhuang, Z.; Xu, G.; Kan, Q. Switching from fatty acid oxidation to glycolysis improves the outcome of acuteonchronic liver failure. Adv. Sci., 2020, 7(7), 1902996.
[http://dx.doi.org/10.1002/advs.201902996] [PMID: 32274306]
[23]
Yamada, N.; Karasawa, T.; Kimura, H.; Watanabe, S.; Komada, T.; Kamata, R.; Sampilvanjil, A.; Ito, J.; Nakagawa, K.; Kuwata, H.; Hara, S.; Mizuta, K.; Sakuma, Y.; Sata, N.; Takahashi, M. Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure. Cell Death Dis., 2020, 11(2), 144.
[http://dx.doi.org/10.1038/s41419-020-2334-2] [PMID: 32094346]
[24]
Arconzo, M.; Piccinin, E.; Moschetta, A. Increased risk of acute liver failure by pain killer drugs in NAFLD: Focus on nuclear receptors and their coactivators. Dig. Liver Dis., 2021, 53(1), 26-34.
[http://dx.doi.org/10.1016/j.dld.2020.05.034] [PMID: 32546444]
[25]
DiPaola, F.; Grimley, M.; Bucuvalas, J. Pediatric acute liver failure and immune dysregulation. J. Pediatr., 2014, 164(2), 407-409.
[http://dx.doi.org/10.1016/j.jpeds.2013.10.044] [PMID: 24315507]
[26]
Saha, R.; Pradhan, S.S. Shalimar; Das, P.; Mishra, P.; Singh, R.; Sivaramakrishnan, V.; Acharya, P. Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177. Sci. Rep., 2021, 11(1), 18849.
[http://dx.doi.org/10.1038/s41598-021-98086-6] [PMID: 34552111]
[27]
Ishikawa, M.; Brooks, A.J.; Fernández-Rojo, M.A.; Medina, J.; Chhabra, Y.; Minami, S.; Tunny, K.A.; Parton, R.G.; Vivian, J.P.; Rossjohn, J.; Chikani, V.; Ramm, G.A.; Ho, K.K.Y.; Waters, M.J. Growth hormone stops excessive inflammation after partial hepatectomy, allowing liver regeneration and survival through induction of H2BL/HLAG. Hepatology, 2021, 73(2), 759-775.
[http://dx.doi.org/10.1002/hep.31297] [PMID: 32342533]
[28]
Triantafyllou, E.; Woollard, K.J.; McPhail, M.J.W.; Antoniades, C.G.; Possamai, L.A. The role of monocytes and macrophages in acute and acute-on-chronic liver failure. Front. Immunol., 2018, 9, 2948.
[http://dx.doi.org/10.3389/fimmu.2018.02948] [PMID: 30619308]
[29]
Starkey Lewis, P.; Campana, L.; Aleksieva, N.; Cartwright, J.A.; Mackinnon, A.; O’Duibhir, E.; Kendall, T.; Vermeren, M.; Thomson, A.; Gadd, V.; Dwyer, B.; Aird, R.; Man, T.Y.; Rossi, A.G.; Forrester, L.; Park, B.K.; Forbes, S.J. Alternatively activated macrophages promote resolution of necrosis following acute liver injury. J. Hepatol., 2020, 73(2), 349-360.
[http://dx.doi.org/10.1016/j.jhep.2020.02.031] [PMID: 32169610]
[30]
Feng, T.; Wei, D.; Li, Q.; Yang, X.; Han, Y.; Luo, Y.; Jiang, Y. Four novel prognostic genes related to prostate cancer identified using co-expression structure network analysis. Front. Genet., 2021, 12, 584164.
[http://dx.doi.org/10.3389/fgene.2021.584164] [PMID: 33927744]
[31]
Zhang, R.; Ai, J.; Wang, J. sun, C.; Lu, H.; He, A.; Li, M.; Liao, Y.; Lei, J.; Zhou, F.; Wu, L.; Liao, W. NCAPG promotes the proliferation of hepatocellular carcinoma through the CKII-dependent regulation of PTEN. J. Transl. Med., 2022, 20(1), 325.
[http://dx.doi.org/10.1186/s12967-022-03519-z] [PMID: 35864529]
[32]
Sha, J.; Li, J.; Zhou, Y.; Yang, J.; Liu, W.; Jiang, S.; Wang, Y.; Zhang, R.; Di, P.; Li, W. The p53/p21/p16 and PI3K/Akt signaling pathways are involved in the ameliorative effects of maltol on Dgalactoseinduced liver and kidney aging and injury. Phytother. Res., 2021, 35(8), 4411-4424.
[http://dx.doi.org/10.1002/ptr.7142] [PMID: 34028092]
[33]
Choi, G.H.; Chong, J.U.; Han, D.H.; Choi, J.S.; Lee, W. J. Robotic hepatectomy: The Korean experience and perspective. Hepatobiliary Surg. Nutr., 2017, 6(4), 230-238.
[http://dx.doi.org/10.21037/hbsn.2017.01.14] [PMID: 28848745]
[34]
Zhang, L.; Yang, X.; Li, X.; Li, C.; Zhao, L.; Zhou, Y.; Hou, H. Butein sensitizes HeLa cells to cisplatin through the AKT and ERK/p38 MAPK pathways by targeting FoxO3a. Int. J. Mol. Med., 2015, 36(4), 957-966.
[http://dx.doi.org/10.3892/ijmm.2015.2324] [PMID: 26310353]
[35]
Li, Y.; Lu, L.; Luo, N.; Wang, Y.Q.; Gao, H.M. Inhibition of PI3K/AKt/mTOR signaling pathway protects against d-galactosamine/lipopolysaccharide-induced acute liver failure by chaperone-mediated autophagy in rats. Biomed. Pharmacother., 2017, 92, 544-553.
[http://dx.doi.org/10.1016/j.biopha.2017.05.037] [PMID: 28577493]

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