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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Research Article

Prognostic Role of Unfolded Protein Response-Related Genes in Hepatocellular Carcinoma

Author(s): Shuqiao Zhang, Xinyu Li, Yilu Zheng, Hao Hu, Jiahui Liu, Shijun Zhang, Chunzhi Tang, Zhuomao Mo and Weihong Kuang*

Volume 24, Issue 8, 2023

Published on: 15 September, 2023

Page: [666 - 683] Pages: 18

DOI: 10.2174/1389203724666230816090504

Price: $65

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Abstract

Aims: To reveal the prognostic role of unfolded protein response (UPR) -related genes in hepatocellular carcinoma (HCC).

Background: Hepatocellular carcinoma is a genetically heterogeneous tumor, and the prediction of its prognosis remains a challenge. Studies elucidating the molecular mechanisms of UPR have rapidly increased. However, the UPR molecular subtype characteristics of the related genes in HCC progression have yet to be thoroughly studied.

Objective: Conducting a comprehensive assessment of the prognostic signature of genes related to the UPR in patients with HCC can advance our understanding of the cellular processes contributing to the progression of HCC and offer innovative strategies in precise therapy.

Methods: Based on the gene expression profiles associated with UPR in HCC, we explored the molecular subtypes mediated by UPR-related genes and constructed a UPR-related genes signature that could precisely predict the prognosis for HCC.

Results: Using microarray data of HCC patients, differentially expressed UPR-related genes (DEGs) were discovered in malignancies and normal tissues. The HCC was classified into two molecular subtypes by the NMF algorithm based on DEGs modification of the UPR. Moreover, we developed a UPR-related model for predicting HCC patients' prognosis. The robustness of the UPR- related model was confirmed in external validation. Moreover, we analyzed immune responses in different risk groups. Analysis of immune functions revealed that Treg, Macrophages, aDCs, and MHC class-I were significantly up-regulated in high-risk HCC. At the same time, cytolytic activity and type I and II INF response were higher in a low-risk subgroup.

Conclusion: This study identified two UPR molecular subtypes of HCC and developed a ten-gene HCC prognostic signature model (EXTL3, PPP2R5B, ZBTB17, CCT3, CCT4, CCT5, GRPEL2, HSP90AA1, PDRG1, and STC2), which can robustly forecast the progression of HCC.

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[1]
Petrick, J.L.; Kelly, S.P.; Altekruse, S.F.; McGlynn, K.A.; Rosenberg, P.S. Future of hepatocellular carcinoma incidence in the united states forecast through 2030. J. Clin. Oncol., 2016, 34(15), 1787-1794.
[http://dx.doi.org/10.1200/JCO.2015.64.7412] [PMID: 27044939]
[2]
Llovet, J.M.; Kelley, R.K.; Villanueva, A.; Singal, A.G.; Pikarsky, E.; Roayaie, S.; Lencioni, R.; Koike, K.; Zucman-Rossi, J.; Finn, R.S. Hepatocellular carcinoma. Nat. Rev. Dis. Primers, 2021, 7(1), 6.
[http://dx.doi.org/10.1038/s41572-020-00240-3] [PMID: 33479224]
[3]
Kim, E.; via tour, P. Hepatocellular carcinoma: Old friends and new tricks. Exp. Mol. Med., 2020, 52(12), 1898-1907.
[http://dx.doi.org/10.1038/s12276-020-00527-1] [PMID: 33268834]
[4]
Mittal, S.; El-Serag, H.B. Epidemiology of hepatocellular carcinoma: Consider the population. J. Clin. Gastroenterol., 2013, 47(0)(Suppl. 1), S2-S6.
[http://dx.doi.org/10.1097/MCG.0b013e3182872f29] [PMID: 23632345]
[5]
Llovet, J.M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, J.F.; de Oliveira, A.C.; Santoro, A.; Raoul, J.L.; Forner, A.; Schwartz, M.; Porta, C.; Zeuzem, S.; Bolondi, L.; Greten, T.F.; Galle, P.R.; Seitz, J.F.; Borbath, I.; Häussinger, D.; Giannaris, T.; Shan, M.; Moscovici, M.; Voliotis, D.; Bruix, J. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med., 2008, 359(4), 378-390.
[http://dx.doi.org/10.1056/NEJMoa0708857] [PMID: 18650514]
[6]
Hetz, C.; Zhang, K.; Kaufman, R.J. Mechanisms, regulation and functions of the unfolded protein response. Nat. Rev. Mol. Cell Biol., 2020, 21(8), 421-438.
[http://dx.doi.org/10.1038/s41580-020-0250-z] [PMID: 32457508]
[7]
Hetz, C.; Chevet, E.; Harding, H.P. Targeting the unfolded protein response in disease. Nat. Rev. Drug Discov., 2013, 12(9), 703-719.
[http://dx.doi.org/10.1038/nrd3976] [PMID: 23989796]
[8]
Ma, Y.; Hendershot, L.M. The role of the unfolded protein response in tumour development: Friend or foe?. Nat. Rev. Cancer, 2004, 4(12), 966-977.
[http://dx.doi.org/10.1038/nrc1505] [PMID: 15573118]
[9]
Zhang, K.; Zheng, Z.; Wang, G.; Li, L.; Tseng, J.; Sun, F.; Chen, X.; Chang, L.; Heng, H. Transcriptional signatures of unfolded protein response implicate the limitation of animal models in pathophysiological studies. Environ. Dis., 2016, 1(1), 24-30.
[http://dx.doi.org/10.4103/2468-5690.180333] [PMID: 28265594]
[10]
Wei, J.; Fang, D. Endoplasmic reticulum stress signaling and the pathogenesis of hepatocarcinoma. Int. J. Mol. Sci., 2021, 22(4), 1799.
[http://dx.doi.org/10.3390/ijms22041799] [PMID: 33670323]
[11]
Kim, J.Y.; Garcia-Carbonell, R.; Yamachika, S.; Zhao, P.; Dhar, D.; Loomba, R.; Kaufman, R.J.; Saltiel, A.R.; Karin, M. ER stress drives lipogenesis and steatohepatitis via caspase-2 activation of s1p. Cell, 2018, 175(1), 133-145.e15.
[http://dx.doi.org/10.1016/j.cell.2018.08.020] [PMID: 30220454]
[12]
Wu, S.; Du, R.; Gao, C.; Kang, J.; Wen, J.; Sun, T. The role of XBP1s in the metastasis and prognosis of hepatocellular carcinoma. Biochem. Biophys. Res. Commun., 2018, 500(3), 530-537.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.033] [PMID: 29627568]
[13]
Pavlović, N.; Calitz, C.; Thanapirom, K.; Mazza, G.; Rombouts, K.; Gerwins, P.; Heindryckx, F. Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma. eLife, 2020, 9, e55865.
[http://dx.doi.org/10.7554/eLife.55865] [PMID: 33103995]
[14]
Vandewynckel, Y.P.; Laukens, D.; Bogaerts, E.; Paridaens, A.; Van den Bussche, A.; Verhelst, X.; Van Steenkiste, C.; Descamps, B.; Vanhove, C.; Libbrecht, L.; De Rycke, R.; Lambrecht, B.N.; Geerts, A.; Janssens, S.; Van Vlierberghe, H. Modulation of the unfolded protein response impedes tumor cell adaptation to proteotoxic stress: A perk for hepatocellular carcinoma therapy. Hepatol. Int., 2015, 9(1), 93-104.
[http://dx.doi.org/10.1007/s12072-014-9582-0] [PMID: 25598862]
[15]
Zhou, B.; Lu, Q.; Liu, J.; Fan, L.; Wang, Y.; Wei, W.; Wang, H.; Sun, G. Melatonin increases the sensitivity of hepatocellular carcinoma to sorafenib through the perk-atf4-beclin1 pathway. Int. J. Biol. Sci., 2019, 15(9), 1905-1920.
[http://dx.doi.org/10.7150/ijbs.32550] [PMID: 31523192]
[16]
Chatterjee, S.; Hirota, H.; Belfi, C.A.; Berger, S.J.; Berger, N.A. Hypersensitivity to dna cross-linking agents associated with up-regulation of glucose-regulated stress protein GRP78. Cancer Res., 1997, 57, 5112-5116. https://www.ncbi.nlm.nih.gov/pubmed/9371511
[17]
Yamada, M.; Tomida, A.; Yun, J.; Cai, B.; Yoshikawa, H.; Taketani, Y.; Tsuruo, T. Cellular sensitization to cisplatin and carboplatin with decreased removal of platinum-DNA adduct by glucose-regulated stress. Cancer Chemother. Pharmacol., 1999, 44(1), 59-64.
[http://dx.doi.org/10.1007/s002800050945] [PMID: 10367750]
[18]
Maurel, M.; McGrath, E.P.; Mnich, K.; Healy, S.; Chevet, E.; Samali, A. Controlling the unfolded protein response-mediated life and death decisions in cancer. Semin. Cancer Biol., 2015, 33, 57-66.
[http://dx.doi.org/10.1016/j.semcancer.2015.03.003] [PMID: 25814342]
[19]
Liberzon, A.; Birger, C.; Thorvaldsdóttir, H.; Ghandi, M.; Mesirov, J.P.; Tamayo, P. The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst., 2015, 1(6), 417-425.
[http://dx.doi.org/10.1016/j.cels.2015.12.004] [PMID: 26771021]
[20]
Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The string database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612.
[http://dx.doi.org/10.1093/nar/gkaa1074] [PMID: 33237311]
[21]
Newman, A.M.; Liu, C.L.; Green, M.R.; Gentles, A.J.; Feng, W.; Xu, Y.; Hoang, C.D.; Diehn, M.; Alizadeh, A.A. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods, 2015, 12(5), 453-457.
[http://dx.doi.org/10.1038/nmeth.3337] [PMID: 25822800]
[22]
Charoentong, P.; Finotello, F.; Angelova, M.; Mayer, C.; Efremova, M.; Rieder, D.; Hackl, H.; Trajanoski, Z. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep., 2017, 18(1), 248-262.
[http://dx.doi.org/10.1016/j.celrep.2016.12.019] [PMID: 28052254]
[23]
Vickers, A.J.; Cronin, A.M.; Elkin, E.B.; Gonen, M. Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med. Inform. Decis. Mak., 2008, 8(1), 53.
[http://dx.doi.org/10.1186/1472-6947-8-53] [PMID: 19036144]
[24]
Rooney, M.S.; Shukla, S.A.; Wu, C.J.; Getz, G.; Hacohen, N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell, 2015, 160(1-2), 48-61.
[http://dx.doi.org/10.1016/j.cell.2014.12.033] [PMID: 25594174]
[25]
Zhang, S.; Li, X.; Zhang, X.; Zhang, S.; Tang, C.; Kuang, W. The pyroptosis-related gene signature predicts the prognosis of hepatocellular carcinoma. Front. Mol. Biosci., 2022, 8, 781427.
[http://dx.doi.org/10.3389/fmolb.2021.781427] [PMID: 35047554]
[26]
Chen, B.; Khodadoust, M.S.; Liu, C.L.; Newman, A.M.; Alizadeh, A.A. Profiling tumor infiltrating immune cells with cibersort. Methods Mol. Biol., 2018, 1711, 243-259.
[http://dx.doi.org/10.1007/978-1-4939-7493-1_12] [PMID: 29344893]
[27]
Wang, L.; Sebra, R.P.; Sfakianos, J.P.; Allette, K.; Wang, W.; Yoo, S.; Bhardwaj, N.; Schadt, E.E.; Yao, X.; Galsky, M.D.; Zhu, J. A reference profile-free deconvolution method to infer cancer cell-intrinsic subtypes and tumor-type-specific stromal profiles. Genome Med., 2020, 12(1), 24.
[http://dx.doi.org/10.1186/s13073-020-0720-0] [PMID: 32111252]
[28]
Plattner, C.; Finotello, F.; Rieder, D. Deconvoluting tumor-infiltrating immune cells from rna-seq data using quantiseq. Methods Enzymol., 2020, 636, 261-285.
[http://dx.doi.org/10.1016/bs.mie.2019.05.056] [PMID: 32178821]
[29]
Shi, J.; Jiang, D.; Yang, S.; Zhang, X.; Wang, J.; Liu, Y.; Sun, Y.; Lu, Y.; Yang, K. LPAR1, correlated with immune infiltrates, is a potential prognostic biomarker in prostate cancer. Front. Oncol., 2020, 10, 846.
[http://dx.doi.org/10.3389/fonc.2020.00846] [PMID: 32656075]
[30]
Aran, D.; Hu, Z.; Butte, A.J. Xcell: Digitally portraying the tissue cellular heterogeneity landscape. Genome Biol., 2017, 18(1), 220.
[http://dx.doi.org/10.1186/s13059-017-1349-1] [PMID: 29141660]
[31]
Racle, J.; de Jonge, K.; Baumgaertner, P.; Speiser, D.E.; Gfeller, D. Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data. eLife, 2017, 6, e26476.
[http://dx.doi.org/10.7554/eLife.26476] [PMID: 29130882]
[32]
Li, T.; Fan, J.; Wang, B.; Traugh, N.; Chen, Q.; Liu, J.S.; Li, B.; Liu, X.S. Timer: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res., 2017, 77(21), e108-e110.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0307] [PMID: 29092952]
[33]
Scholer, A; Garland-Kledzik, M; Ghosh, D; Santamaria-Barria, J; Khader, A; Orozco, J Exploring the genomic landscape of hepatobiliary cancers to establish a novel molecular subtype classification. J. clin. oncol., 2020, 38, 562.
[http://dx.doi.org/10.1200/JCO.2020.38.4_suppl.562]
[34]
Zhang, Q.; Yu, X.; Zheng, Q.; He, Y.; Guo, W. A molecular subtype model for liver hbv-related hepatocellular carcinoma patients based on immune-related genes. Front. Oncol., 2020, 10, 560229.
[http://dx.doi.org/10.3389/fonc.2020.560229] [PMID: 33072587]
[35]
Yan, Y.; Lu, Y.; Mao, K.; Zhang, M.; Liu, H.; Zhou, Q.; Lin, J.; Zhang, J.; Wang, J.; Xiao, Z. Identification and validation of a prognostic four-genes signature for hepatocellular carcinoma: Integrated cerna network analysis. Hepatol. Int., 2019, 13(5), 618-630.
[http://dx.doi.org/10.1007/s12072-019-09962-3] [PMID: 31321712]
[36]
Wu, G.; Yang, Y.; Zhu, Y.; Li, Y.; Zhai, Z.; An, L.; Liu, M.; Zheng, Y.; Wang, Y.; Zhou, Y.; Guo, Q. Comprehensive analysis to identify the epithelial–mesenchymal transition-related immune signatures as a prognostic and therapeutic biomarkers in hepatocellular carcinoma. Front. Surg., 2021, 8, 742443.
[http://dx.doi.org/10.3389/fsurg.2021.742443] [PMID: 34722623]
[37]
Liang, J.; Wang, D.; Lin, H.; Chen, X.; Yang, H.; Zheng, Y.; Li, Y. A novel ferroptosis-related gene signature for overall survival prediction in patients with hepatocellular carcinoma. Int. J. Biol. Sci., 2020, 16(13), 2430-2441.
[http://dx.doi.org/10.7150/ijbs.45050] [PMID: 32760210]
[38]
Liu, Z.; Jiao, D.; Liu, L.; Zhou, X.; Yao, Y.; Li, Z.; Li, J.; Chen, J.; Lei, Q.; Han, X. Development and validation of a robust immune-related risk signature for hepatocellular carcinoma. Medicine, 2021, 100(10), e24683.
[http://dx.doi.org/10.1097/MD.0000000000024683] [PMID: 33725827]
[39]
Li, B.; Feng, W.; Luo, O.; Xu, T.; Cao, Y.; Wu, H.; Yu, D.; Ding, Y. Development and validation of a three-gene prognostic signature for patients with hepatocellular carcinoma. Sci. Rep., 2017, 7(1), 5517.
[http://dx.doi.org/10.1038/s41598-017-04811-5] [PMID: 28717245]
[40]
Corazzari, M.; Gagliardi, M.; Fimia, G.M.; Piacentini, M. endoplasmic reticulum stress, unfolded protein response, and cancer cell fate. Front. Oncol., 2017, 7, 78.
[http://dx.doi.org/10.3389/fonc.2017.00078] [PMID: 28491820]
[41]
Ojha, R.; Amaravadi, R.K. Targeting the unfolded protein response in cancer. Pharmacol. Res., 2017, 120, 258-266.
[http://dx.doi.org/10.1016/j.phrs.2017.04.003] [PMID: 28396092]
[42]
Wang, M.; Law, M.E.; Castellano, R.K.; Law, B.K. The unfolded protein response as a target for anticancer therapeutics. Crit. Rev. Oncol. Hematol., 2018, 127, 66-79.
[http://dx.doi.org/10.1016/j.critrevonc.2018.05.003] [PMID: 29891114]
[43]
Hazari, Y.M.; Bashir, A.; Haq, E.; Fazili, K.M. Emerging tale of upr and cancer: An essentiality for malignancy. Tumour Biol., 2016, 37(11), 14381-14390.
[http://dx.doi.org/10.1007/s13277-016-5343-0] [PMID: 27629140]
[44]
Clarke, H.J.; Chambers, J.E.; Liniker, E.; Marciniak, S.J. Endoplasmic reticulum stress in malignancy. Cancer Cell, 2014, 25(5), 563-573.
[http://dx.doi.org/10.1016/j.ccr.2014.03.015] [PMID: 24823636]
[45]
Chevet, E.; Hetz, C.; Samali, A. Endoplasmic reticulum stress-activated cell reprogramming in oncogenesis. Cancer Discov., 2015, 5(6), 586-597.
[http://dx.doi.org/10.1158/2159-8290.CD-14-1490] [PMID: 25977222]
[46]
Strzyz, P. Pro-survival clock supression. Nat. Rev. Mol. Cell Biol., 2018, 19(2), 74-75.
[http://dx.doi.org/10.1038/nrm.2017.137] [PMID: 29259333]
[47]
Koumenis, C. ER stress, hypoxia tolerance and tumor progression. Curr. Mol. Med., 2006, 6(1), 55-69.
[http://dx.doi.org/10.2174/156652406775574604] [PMID: 16472113]
[48]
Moenner, M.; Pluquet, O.; Bouchecareilh, M.; Chevet, E. Integrated endoplasmic reticulum stress responses in cancer. Cancer Res., 2007, 67(22), 10631-10634.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1705] [PMID: 18006802]
[49]
Cho, C.; Horzempa, C.; Jones, D.; McKeown-Longo, P.J. The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and trail resistance in human lung cancer cells. BMC Cancer, 2016, 16(1), 574.
[http://dx.doi.org/10.1186/s12885-016-2621-6] [PMID: 27484721]
[50]
Chen, G.; Wu, J.; Su, Z.; Wang, L.; Chen, X.; Zhong, X.; Wang, D.; Wang, J.; Shao, L. An unfolded protein response-related mrna signature predicting the survival and therapeutic effect of hepatocellular carcinoma. Comb. Chem. High Throughput Screen., 2022, 25(12), 2046-2058.
[http://dx.doi.org/10.2174/1386207325666220204140925] [PMID: 35125080]
[51]
Houessinon, A.; Gicquel, A.; Bochereau, F.; Louandre, C.; Nyga, R.; Godin, C.; Degonville, J.; Fournier, E.; Saidak, Z.; Drullion, C.; Barbare, J.C.; Chauffert, B.; François, C.; Pluquet, O.; Galmiche, A. Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib. Cancer Lett., 2016, 370(2), 242-249.
[http://dx.doi.org/10.1016/j.canlet.2015.10.032] [PMID: 26546044]
[52]
Kanda, M.; Sadakari, Y.; Borges, M.; Topazian, M.; Farrell, J.; Syngal, S.; Lee, J.; Kamel, I.; Lennon, A.M.; Knight, S.; Fujiwara, S.; Hruban, R.H.; Canto, M.I.; Goggins, M. Mutant tp53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin. Gastroenterol. Hepatol., 2013, 11(6), 719-730.e5.
[http://dx.doi.org/10.1016/j.cgh.2012.11.016] [PMID: 23200980]
[53]
Leroy, B.; Anderson, M.; Soussi, T. TP53 mutations in human cancer: Database reassessment and prospects for the next decade. Hum. Mutat., 2014, 35(6), 672-688.
[http://dx.doi.org/10.1002/humu.22552] [PMID: 24665023]
[54]
Patel, A.; Oshi, M.; Yan, L.; Matsuyama, R.; Endo, I.; Takabe, K. The Unfolded protein response is associated with cancer proliferation and worse survival in hepatocellular carcinoma. Cancers, 2021, 13(17), 4443.
[http://dx.doi.org/10.3390/cancers13174443] [PMID: 34503253]
[55]
Arai, T.; Akiyama, Y.; Nagasaki, H.; Murase, N.; Okabe, S.; Ikeuchi, T.; Saito, K.; Iwai, T.; Yuasa, Y. EXTL3/EXTR1 alterations in colorectal cancer cell lines. Int. J. Oncol., 1999, 15(5), 915-919.
[http://dx.doi.org/10.3892/ijo.15.5.915] [PMID: 10536173]
[56]
Cunningham, C.E.; Li, S.; Vizeacoumar, F.S.; Bhanumathy, K.K.; Lee, J.S.; Parameswaran, S.; Furber, L.; Abuhussein, O.; Paul, J.M.; McDonald, M.; Templeton, S.D.; Shukla, H.; El Zawily, A.M.; Boyd, F.; Alli, N.; Mousseau, D.D.; Geyer, R.; Bonham, K.; Anderson, D.H.; Yan, J.; Yu-Lee, L.Y.; Weaver, B.A.; Uppalapati, M.; Ruppin, E.; Sablina, A.; Freywald, A.; Vizeacoumar, F.J. Therapeutic relevance of the protein phosphatase 2A in cancer. Oncotarget, 2016, 7(38), 61544-61561.
[http://dx.doi.org/10.18632/oncotarget.11399] [PMID: 27557495]
[57]
Kress, T.R.; Pellanda, P.; Pellegrinet, L.; Bianchi, V.; Nicoli, P.; Doni, M.; Recordati, C.; Bianchi, S.; Rotta, L.; Capra, T.; Ravà, M.; Verrecchia, A.; Radaelli, E.; Littlewood, T.D.; Evan, G.I.; Amati, B. Identification of myc-dependent transcriptional programs in oncogene-addicted liver tumors. Cancer Res., 2016, 76(12), 3463-3472.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0316] [PMID: 27197165]
[58]
Liu, Y.; Zhang, X.; Lin, J.; Chen, Y.; Qiao, Y.; Guo, S.; Yang, Y.; Zhu, G.; Pan, Q.; Wang, J.; Sun, F. CCT3 acts upstream of yap and tfcp2 as a potential target and tumour biomarker in liver cancer. Cell Death Dis., 2019, 10(9), 644.
[http://dx.doi.org/10.1038/s41419-019-1894-5] [PMID: 31501420]
[59]
Sergeeva, O.A.; Chen, B.; Haase-Pettingell, C.; Ludtke, S.J.; Chiu, W.; King, J.A. Human CCT4 and CCT5 chaperonin subunits expressed in Escherichia coli form biologically active homo-oligomers. J. Biol. Chem., 2013, 288(24), 17734-17744.
[http://dx.doi.org/10.1074/jbc.M112.443929] [PMID: 23612981]
[60]
Lai, M.C.; Zhu, Q.Q.; Xu, J.; Zhang, W.J. Experimental and clinical evidence suggests that grpel2 plays an oncogenic role in hcc development. Am. J. Cancer Res., 2021 sep 15;11(9), 4175-4198.https://www.ncbi.nlm.nih.gov/pubmed/34659882
[61]
Xiao, H.; Wang, B.; Xiong, H.X.; Guan, J.F.; Wang, J.; Tan, T.; Lin, K.; Zou, S.B.; Hu, Z.G.; Wang, K. A novel prognostic index of hepatocellular carcinoma based on immunogenomic landscape analysis. J. Cell. Physiol., 2021, 236(4), 2572-2591.
[http://dx.doi.org/10.1002/jcp.30015] [PMID: 32853412]
[62]
Jiang, L.; Luo, X.; Shi, J.; Sun, H.; Sun, Q.; Sheikh, M.S.; Huang, Y. PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress. Cancer Biol. Ther., 2011, 11(6), 567-573.
[http://dx.doi.org/10.4161/cbt.11.6.14412] [PMID: 21193842]
[63]
Li, S.; Huang, Q.; Li, D.; Lv, L.; Li, Y.; Wu, Z. The significance of Stanniocalcin 2 in malignancies and mechanisms. Bioengineered, 2021, 12(1), 7276-7285.
[http://dx.doi.org/10.1080/21655979.2021.1977551] [PMID: 34612765]
[64]
Janssens, S.; Pulendran, B.; Lambrecht, B.N. Emerging functions of the unfolded protein response in immunity. Nat. Immunol., 2014, 15(10), 910-919.
[http://dx.doi.org/10.1038/ni.2991] [PMID: 25232821]
[65]
Hsu, S.K.; Chiu, C.C.; Dahms, H.U.; Chou, C.K.; Cheng, C.M.; Chang, W.T.; Cheng, K.C.; Wang, H.M.D.; Lin, I.L. Unfolded protein response (upr) in survival, dormancy, immunosuppression, metastasis, and treatments of cancer cells. Int. J. Mol. Sci., 2019, 20(10), 2518.
[http://dx.doi.org/10.3390/ijms20102518] [PMID: 31121863]
[66]
Keir, M.E.; Butte, M.J.; Freeman, G.J.; Sharpe, A.H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol., 2008, 26(1), 677-704.
[http://dx.doi.org/10.1146/annurev.immunol.26.021607.090331] [PMID: 18173375]
[67]
Chen, J.; Jiang, C.C.; Jin, L.; Zhang, X.D. Regulation of PD-L1: A novel role of pro-survival signalling in cancer. Ann. Oncol., 2016, 27(3), 409-416.
[http://dx.doi.org/10.1093/annonc/mdv615] [PMID: 26681673]
[68]
Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12(4), 252-264.
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[69]
Ivashkiv, L.B.; Donlin, L.T. Regulation of type I interferon responses. Nat. Rev. Immunol., 2014, 14(1), 36-49.
[http://dx.doi.org/10.1038/nri3581] [PMID: 24362405]
[70]
Sharpe, A.H.; Wherry, E.J.; Ahmed, R.; Freeman, G.J. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat. Immunol., 2007, 8(3), 239-245.
[http://dx.doi.org/10.1038/ni1443] [PMID: 17304234]
[71]
Clarke, R.; Cook, K.L. Unfolding the role of stress response signaling in endocrine resistant breast cancers. Front. Oncol., 2015, 5, 140.
[http://dx.doi.org/10.3389/fonc.2015.00140] [PMID: 26157705]
[72]
Huang, H.; Weng, H.; Chen, J. m6A modification in coding and non-coding rnas: Roles and therapeutic implications in cancer. Cancer Cell, 2020, 37(3), 270-288.
[http://dx.doi.org/10.1016/j.ccell.2020.02.004] [PMID: 32183948]

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