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Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta as a potential biomarker for Opisthorchis viverrini infection and cholangiocarcinoma

Published online by Cambridge University Press:  05 October 2021

Sattrachai Prasopdee ,
Yodying Yingchutrakul ,
Sittiruk Roytrakul ,
Montinee Pholhelm ,
Teva Phanaksri ,
Anthicha Kunjantarachot ,
Jutharat Kulsantiwong ,
Kritiya Butthongkomvong ,
Smarn Tesana  and
Thanakrit Sathavornmanee
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Sattrachai Prasopdee
Affiliation:
Thammasat University Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected Parasitic Diseases, Thammasat University, Pathum Thani, 12120, Thailand Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand
Yodying Yingchutrakul
Affiliation:
Proteomics Research Team, National Omics Center, NSTDA, Pathum Thani, 12120, Thailand
Sittiruk Roytrakul
Affiliation:
Proteomics Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, Pathum Thani, 12120, Thailand
Montinee Pholhelm
Affiliation:
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand
Teva Phanaksri
Affiliation:
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand
Anthicha Kunjantarachot
Affiliation:
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand
Jutharat Kulsantiwong
Affiliation:
Faculty of Science, Udon Thani Rajabhat University, Udon Thani, 41000, Thailand
Kritiya Butthongkomvong
Affiliation:
Medical Oncology Unit, Udonthani Cancer Hospital, Udon Thani, 41330, Thailand
Smarn Tesana
Affiliation:
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand
Thanakrit Sathavornmanee
Affiliation:
Chonburi hospital, Ministry of Public Health, Chonburi, 20000, Thailand
Veerachai Thitapakorn*
Affiliation:
Thammasat University Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected Parasitic Diseases, Thammasat University, Pathum Thani, 12120, Thailand Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand
*
Author for correspondence: Veerachai Thitapakorn, E-mail: veebkk@gmail.com
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Abstract

The human liver fluke Opisthorchis viverrini (Ov), the primary risk factor for cholangiocarcinoma (CHCA), is a parasite endemic to southeast Asian countries. With no effective treatments for CHCA currently available, early diagnosis and treatment of Ov infection remains the only practical method for the prevention of CHCA. In this study, plasma phosphoproteomes of patients in the non-Ov infection, non-cholangiocarcinoma subject group (non-OVCCA), the asymptomatic Ov infected group (OV), and the CHCA group (CCA), were investigated to identify potential biomarkers for Ov infection and CHCA. The AKT signalling pathway was found to be up-regulated. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB), an upstream signalling molecule, was selected as a potential biomarker and evaluated using indirect enzyme-linked immunosorbent assay (ELISA). Results demonstrated evidence that levels of PIK3CB in both the OV group and CCA group was statistically different compared to the non-OVCCA group (P < 0.01). However, the levels of PIK3CB between the OV group and the CCA group were found not to be statistically different. Sensitivity and specificity for OV using OD450 cut-off at >1.570 was 76 and 72%, respectively. For CCA, sensitivity and specificity using OD450 cut-off at >1.398 was 68 and 76%, respectively. Application of indirect ELISA detecting plasma PIK3CB will be of great benefit for screening of opisthorchiasis and CHCA.

Keywords

BiomarkercholangiocarcinomadiagnosisOpisthorchis viverriniPhosphoproteomePIK3CB
Type
Research Article
Information
Parasitology , Volume 149 , Issue 2 , February 2022 , pp. 171 - 180
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Banales, JM, Marin, JJG, Lamarca, A, Rodrigues, PM, Khan, SA, Roberts, LR, Cardinale, V, Carpino, G, Andersen, JB, Braconi, C, Calvisi, DF, Perugorria, MJ, Fabris, L, Boulter, L, Macias, RIR, Gaudio, E, Alvaro, D, Gradilone, SA, Strazzabosco, M, Marzioni, M, Coulouarn, C, Fouassier, L, Raggi, C, Invernizzi, P, Mertens, JC, Moncsek, A, Rizvi, S, Heimbach, J, Koerkamp, BG, Bruix, J, Forner, A, Bridgewater, J, Valle, JW and Gores, GJ (2020) Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nature Reviews. Gastroenterology & Hepatology 17, 557–588.CrossRefGoogle ScholarPubMed
Bardou, P, Mariette, J, Escudie, F, Djemiel, C and Klopp, C (2014) jvenn: an interactive Venn diagram viewer. BMC Bioinformatics 15, 293.CrossRefGoogle ScholarPubMed
Bommarito, D, Martin, A, Forcade, E, Nastke, MD, Ritz, J and Bellucci, R (2016) Enhancement of tumor cell susceptibility to natural killer cell activity through inhibition of the PI3K signaling pathway. Cancer Immunology Immunotherapy 65, 355–366.CrossRefGoogle ScholarPubMed
Brognard, J, Sierecki, E, Gao, T and Newton, AC (2007) PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Molecular Cell 25, 917–931.CrossRefGoogle Scholar
Carnero, A and Paramio, JM (2014) The PTEN/PI3K/AKT pathway in vivo, cancer mouse models. Frontiers in Oncology 4, 252.CrossRefGoogle ScholarPubMed
Corti, F, Nichetti, F, Raimondi, A, Niger, M, Prinzi, N, Torchio, M, Tamborini, E, Perrone, F, Pruneri, G, Di Bartolomeo, M, de Braud, F and Pusceddu, S (2019) Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: a review of current evidences and future perspectives. Cancer Treatment Reviews 72, 45–55.CrossRefGoogle ScholarPubMed
Daorueang, D, Thuwajit, P, Roitrakul, S, Laha, T, Kaewkes, S, Endo, Y and Thuwajit, C (2012) Secreted Opisthorchis viverrini glutathione S-transferase regulates cell proliferation through AKT and ERK pathways in cholangiocarcinoma. Parasitology International 61, 155–161.CrossRefGoogle ScholarPubMed
Dokduang, H, Juntana, S, Techasen, A, Namwat, N, Yongvanit, P, Khuntikeo, N, Riggins, GJ and Loilome, W (2013) Survey of activated kinase proteins reveals potential targets for cholangiocarcinoma treatment. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 34, 3519–3528.CrossRefGoogle ScholarPubMed
Duan, HX, Li, BW, Zhuang, X, Wang, LT, Cao, Q, Tan, LH, Qu, GF and Xiao, S (2019) TCF21 Inhibits tumor-associated angiogenesis and suppresses the growth of cholangiocarcinoma by targeting PI3K/Akt and ERK signaling. American Journal of Physiology. Gastrointestinal and Liver Physiology 316, G763–G773.CrossRefGoogle ScholarPubMed
Elmenier, FM, Lasheen, DS and Abouzid, KAM (2019) Phosphatidylinositol 3 kinase (PI3K) inhibitors as new weapon to combat cancer. European Journal of Medicinal Chemistry 183, 111718.CrossRefGoogle ScholarPubMed
Ersahin, T, Tuncbag, N and Cetin-Atalay, R (2015) The PI3K/AKT/mTOR interactive pathway. Molecular BioSystems 11, 1946–1954.CrossRefGoogle ScholarPubMed
Ewald, F, Grabinski, N, Grottke, A, Windhorst, S, Norz, D, Carstensen, L, Staufer, K, Hofmann, BT, Diehl, F, David, K, Schumacher, U, Nashan, B and Jucker, M (2013) Combined targeting of AKT and mTOR using MK-2206 and RAD001 is synergistic in the treatment of cholangiocarcinoma. International Journal of Cancer 133, 2065–2076.CrossRefGoogle ScholarPubMed
IARC (1994) Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 61, 121–175.Google Scholar
Johansson, C, Samskog, J, Sundstrom, L, Wadensten, H, Bjorkesten, L and Flensburg, J (2006) Differential expression analysis of Escherichia coli proteins using a novel software for relative quantitation of LC-MS/MS data. Proteomics 6, 4475–4485.CrossRefGoogle ScholarPubMed
Klungsaeng, S, Kukongviriyapan, V, Prawan, A, Kongpetch, S and Senggunprai, L (2019) Cucurbitacin B induces mitochondrial-mediated apoptosis pathway in cholangiocarcinoma cells via suppressing focal adhesion kinase signaling. Naunyn-Schmiedeberg's Archives of Pharmacology 392, 271–278.CrossRefGoogle ScholarPubMed
Kumar, A, Redondo-Munoz, J, Perez-Garcia, V, Cortes, I, Chagoyen, M and Carrera, AC (2011) Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival. Molecular and Cellular Biology 31, 2122–2133.CrossRefGoogle ScholarPubMed
Leelawat, K, Udomchaiprasertkul, W, Narong, S and Leelawat, S (2010) Induction of MKP-1 prevents the cytotoxic effects of PI3K inhibition in hilar cholangiocarcinoma cells. Journal of Cancer Research and Clinical Oncology 136, 1537–1544.CrossRefGoogle ScholarPubMed
Maemura, K, Natsugoe, S and Takao, S (2014) Molecular mechanism of cholangiocarcinoma carcinogenesis. Journal of Hepato-Biliary-Pancreatic Sciences 21, 754–760.CrossRefGoogle ScholarPubMed
Mairiang, E (2017) Ultrasonographic features of hepatobiliary pathology in opisthorchiasis and opisthorchiasis-associated cholangiocarcinoma. Parasitology International 66, 378–382.CrossRefGoogle ScholarPubMed
Moolthiya, P, Tohtong, R, Keeratichamroen, S and Leelawat, K (2014) Role of mTOR inhibitor in cholangiocarcinoma cell progression. Oncology Letters 7, 854–860.CrossRefGoogle ScholarPubMed
Murata, M (2018) Inflammation and cancer. Environmental Health and Preventive Medicine 23, 50.CrossRefGoogle ScholarPubMed
Pei, YF, Liu, J, Cheng, J, Wu, WD and Liu, XQ (2019) Silencing of LAMC2 reverses epithelial-mesenchymal transition and inhibits angiogenesis in cholangiocarcinoma via inactivation of the epidermal growth factor receptor signaling pathway. American Journal of Pathology 189, 1637–1653.CrossRefGoogle ScholarPubMed
Perkins, DN, Pappin, DJ, Creasy, DM and Cottrell, JS (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551–3567.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Roninson, IB, Broude, EV and Chang, BD (2001) If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy 4, 303–313.CrossRefGoogle ScholarPubMed
Sang, H, Li, T, Li, H and Liu, J (2015) Gab1 regulates proliferation and migration through the PI3K/Akt signaling pathway in intrahepatic cholangiocarcinoma. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 36, 8367–8377.CrossRefGoogle ScholarPubMed
Shen, H, Zhang, J, Zhang, Y, Feng, Q, Wang, H, Li, G, Jiang, W and Li, X (2019) Knockdown of tripartite motif 59 (TRIM59) inhibits proliferation in cholangiocarcinoma via the PI3K/AKT/mTOR signalling pathway. Gene 698, 50–60.CrossRefGoogle ScholarPubMed
Singh, P, Dar, MS and Dar, MJ (2016) p110alpha and p110beta isoforms of PI3K signaling: are they two sides of the same coin? FEBS Letters 590, 3071–3082.CrossRefGoogle ScholarPubMed
Sohal, DP, Shrotriya, S, Abazeed, M, Cruise, M and Khorana, A (2016) Molecular characteristics of biliary tract cancer. Critical Reviews in Oncology/Hematology 107, 111–118.CrossRefGoogle ScholarPubMed
Szklarczyk, D, Morris, JH, Cook, H, Kuhn, M, Wyder, S, Simonovic, M, Santos, A, Doncheva, NT, Roth, A, Bork, P, Jensen, LJ and von Mering, C (2017) The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Research 45, D362–D368.CrossRefGoogle ScholarPubMed
Tan, ES, Cao, B, Kim, J, Al-Toubah, TE, Mehta, R, Centeno, BA and Kim, RD (2021) Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers. Cancer 127, 1293–1300.CrossRefGoogle ScholarPubMed
Tiemin, P, Fanzheng, M, Peng, X, Jihua, H, Ruipeng, S, Yaliang, L, Yan, W, Junlin, X, Qingfu, L, Zhefeng, H, Jian, L, Zihao, G, Guoxing, L, Boshi, S, Ming, Z, Qinghui, M, Desen, L and Lianxin, L (2020) MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways. Journal of Hepatology 72, 761–773.CrossRefGoogle ScholarPubMed
UniProt, C (2019) UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research 47, D506–D515.Google Scholar
Wang, C, Lei, H, Tian, Y, Shang, M, Wu, Y, Li, Y, Zhao, L, Shi, M, Tang, X, Chen, T, Lv, Z, Huang, Y, Tang, X, Yu, X and Li, X (2017) Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma. Parasites & Vectors 10, 262.CrossRefGoogle ScholarPubMed
Yothaisong, S, Dokduang, H, Techasen, A, Namwat, N, Yongvanit, P, Bhudhisawasdi, V, Puapairoj, A, Riggins, GJ and Loilome, W (2013) Increased activation of PI3K/AKT signaling pathway is associated with cholangiocarcinoma metastasis and PI3K/mTOR inhibition presents a possible therapeutic strategy. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 34, 3637–3648.CrossRefGoogle ScholarPubMed
Yothaisong, S, Thanee, M, Namwat, N, Yongvanit, P, Boonmars, T, Puapairoj, A and Loilome, W (2014) Opisthorchis viverrini infection activates the PI3K/AKT/PTEN and Wnt/beta-catenin signaling pathways in a Cholangiocarcinogenesis model. Asian Pacific Journal of Cancer Prevention: APJCP 15, 10463–10468.CrossRefGoogle Scholar
Yothaisong, S, Namwat, N, Yongvanit, P, Khuntikeo, N, Puapairoj, A, Jutabha, P, Anzai, N, Tassaneeyakul, W, Tangsucharit, P and Loilome, W (2017) Increase in L-type amino acid transporter 1 expression during cholangiocarcinogenesis caused by liver fluke infection and its prognostic significance. Parasitology International 66, 471–478.CrossRefGoogle ScholarPubMed
Zhang, Y, Ji, G, Han, S, Shao, Z, Lu, Z, Huo, L, Zhang, J, Yang, R, Feng, Q, Shen, H, Wang, H and Li, X (2018) Tip60 suppresses cholangiocarcinoma proliferation and metastasis via PI3k-AKT. Cellular Physiology and Biochemistry 50, 612–628.CrossRefGoogle ScholarPubMed
Zhao, X, Luo, G, Cheng, Y, Yu, W, Chen, R, Xiao, B, Xiang, Y, Feng, C, Fu, W, Duan, C, Yao, F, Xia, X, Tao, Q, Wei, M and Dai, R (2018) Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR-independent pathway. Journal of Cellular Biochemistry 119, 5538–5550.CrossRefGoogle Scholar
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