{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:44:03Z","timestamp":1770288243165,"version":"3.49.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Tianjin Health Science and Technology Project","award":["NoTJWJ2021ZD010"],"award-info":[{"award-number":["NoTJWJ2021ZD010"]}]},{"name":"Tianjin Health Science and Technology Project","award":["NoTJWJ2021ZD010"],"award-info":[{"award-number":["NoTJWJ2021ZD010"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Due to the high heterogeneity, the early diagnosis and prognostic prediction of hepatic cellular cancer (HCC) is challenging. In this study, we explored the diagnostic and prognostic value of pyroptosis-related genes (PRGs) in HCC. We downloaded the mRNA expression profiles of HCC and the corresponding clinical data from the TCGA and ICGC databases. Fifty-one PRGs were extracted from Genecards, MsigDB, and relevant literature. The area under the receiver operating characteristic (AUC) was used to explore the diagnostic value of the PRGs.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The results revealed that <jats:italic>BAK1, BAX, CHMP2A, CHMP4C, CHMP6, GSDMC<\/jats:italic>, and <jats:italic>GSDMD<\/jats:italic> had higher diagnostic values for HCC (AUCs\u2009&gt;\u20090.8, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Then, univariate and multivariate analyses of 51 PRGs were performed for HCC samples, and 4 PRGs (<jats:italic>TP53, GPX4, GSDMC, BAK1<\/jats:italic>) associated with HCC prognosis were obtained and used to construct a pyroptosis-related risk model. HCC samples were divided into high-risk and low-risk groups based on the risk score\u2019s cut-off. Kaplan\u2013Meier curve and Log-rank test were used to compare the overall survival (OS) of two risk groups. The OS was lower in the high-risk group than in the low-risk group. In addition, the time-dependent receiver operating characteristics revealed that the risk model could be used to predict the prognosis of HCC more accurately. The risk score also resulted as an independent risk factor for HCC prognosis (TCGA: HR\u2009=\u20092.45, 95% CI 1.53\u20133.92; ICGC: HR\u2009=\u20092.19, 95% CI 1.39\u20133.46). Moreover, the AUC of the risk score for diagnosing HCC was relatively higher (TCGA: AUC\u2009=\u20090.840, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05; ICGC: AUC\u2009=\u20090.795, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In a word, <jats:italic>BAK1, BAX, CHMP2A, CHMP4C, CHMP6, GSDMC, GSDMD<\/jats:italic>, and the pyroptosis-related risk model could be used to diagnose the HCC, and the risk score also resulted as an independent risk factor for the HCC prognosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-022-04726-7","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T08:04:09Z","timestamp":1652429049000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Diagnostic and prognostic values of pyroptosis-related genes for the hepatocellular carcinoma"],"prefix":"10.1186","volume":"23","author":[{"given":"Mindan","family":"Xing","sequence":"first","affiliation":[]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"4726_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"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\u2013424.","journal-title":"CA Cancer J Clin"},{"key":"4726_CR2","unstructured":"China MAaMABotNHCotPsRo. Practice guidelines for diagnosis and treatment of primary hepatic carcinoma(v.2019). Chin J Hepatol 2020;2:112\u201328."},{"key":"4726_CR3","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1055\/s-0038-1676806","volume":"39","author":"YM Yang","year":"2019","unstructured":"Yang YM, Kim SY, Seki E. Inflammation and liver cancer: molecular mechanisms and therapeutic targets. Semin Liver Dis. 2019;39:26\u201342.","journal-title":"Semin Liver Dis"},{"key":"4726_CR4","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/978-3-030-21540-8_4","volume-title":"Hepatocellular carcinoma: translational precision medicine approaches","author":"N Vietti Violi","year":"2019","unstructured":"Vietti Violi N, Lewis S, Hectors S, Said D, Taouli B. Radiological diagnosis and characterization of HCC. In: Hoshida Y, editor. Hepatocellular carcinoma: translational precision medicine approaches. Humana Press: Cham; 2019. p. 71\u201392."},{"key":"4726_CR5","doi-asserted-by":"publisher","first-page":"109052","DOI":"10.1016\/j.cbi.2020.109052","volume":"323","author":"JW Ruan","year":"2020","unstructured":"Ruan JW, Wang SJ, Wang JB. Mechanism and regulation of pyroptosis-mediated in cancer cell death. Chemico-Biol Interact. 2020;323:109052.","journal-title":"Chemico-Biol Interact"},{"key":"4726_CR6","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.tcb.2017.05.005","volume":"27","author":"SB Kovacs","year":"2017","unstructured":"Kovacs SB, Miao EA. Gasdermins: effectors of pyroptosis. Trends Cell Biol. 2017;27:673\u201384.","journal-title":"Trends Cell Biol"},{"key":"4726_CR7","doi-asserted-by":"publisher","first-page":"109595","DOI":"10.1016\/j.biopha.2019.109595","volume":"121","author":"Y Fang","year":"2020","unstructured":"Fang Y, Tian S, Pan Y, Li W, Wang Q, Tang Y, et al. Pyroptosis: a new frontier in cancer. Biomed Pharmacother. 2020;121:109595.","journal-title":"Biomed Pharmacother"},{"key":"4726_CR8","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.7150\/ijbs.24347","volume":"14","author":"F Wang","year":"2018","unstructured":"Wang F, Li G, Ning J, Chen L, Xu H, Kong X, et al. Alcohol accumulation promotes esophagitis via pyroptosis activation. Int J Biol Sci. 2018;14:1245\u201355.","journal-title":"Int J Biol Sci"},{"key":"4726_CR9","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/1751-2980.12576","volume":"19","author":"WJ Wang","year":"2018","unstructured":"Wang WJ, Chen D, Jiang MZ, Xu B, Li XW, Chu Y, et al. Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins. J Dig Dis. 2018;19:74\u201383.","journal-title":"J Dig Dis"},{"key":"4726_CR10","doi-asserted-by":"publisher","first-page":"BSR20171150","DOI":"10.1042\/BSR20171150","volume":"38","author":"J Li","year":"2018","unstructured":"Li J, Yang C, Li Y, Chen A, Li L, You Z. LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation. Biosci Rep. 2018;38:BSR20171150.","journal-title":"Biosci Rep"},{"key":"4726_CR11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.lfs.2019.02.060","volume":"223","author":"HT Guo","year":"2019","unstructured":"Guo HT, Xie MJ, Zhou C, Zheng M. The relevance of pyroptosis in the pathogenesis of liver diseases. Life Sci. 2019;223:69\u201373.","journal-title":"Life Sci"},{"key":"4726_CR12","doi-asserted-by":"publisher","first-page":"827","DOI":"10.3727\/096504018X15462920753012","volume":"27","author":"Q Wei","year":"2019","unstructured":"Wei Q, Zhu R, Zhu J, Zhao R, Li M. E2-induced activation of the NLRP3 inflammasome triggers pyroptosis and inhibits autophagy in HCC cells. Oncol Res. 2019;27:827\u201334.","journal-title":"Oncol Res"},{"key":"4726_CR13","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/labinvest.2013.126","volume":"94","author":"Q Wei","year":"2014","unstructured":"Wei Q, Mu K, Li T, Zhang Y, Yang Z, Jia X, et al. Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression. Lab Invest. 2014;94:52\u201362.","journal-title":"Lab Invest"},{"key":"4726_CR14","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41420-021-00451-x","volume":"7","author":"Y Ye","year":"2021","unstructured":"Ye Y, Dai Q, Qi H. A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer. Cell Death Discov. 2021;7:71.","journal-title":"Cell Death Discov"},{"key":"4726_CR15","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/s41419-019-1883-8","volume":"10","author":"X Xia","year":"2019","unstructured":"Xia X, Wang X, Cheng Z, Qin W, Lei L, Jiang J, et al. The role of pyroptosis in cancer: pro-cancer or pro-\"host\"? Cell Death Dis. 2019;10:650.","journal-title":"Cell Death Dis"},{"key":"4726_CR16","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41568-019-0123-y","volume":"19","author":"R Karki","year":"2019","unstructured":"Karki R, Kanneganti TD. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat Rev Cancer. 2019;19:197\u2013214.","journal-title":"Nat Rev Cancer"},{"key":"4726_CR17","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.jsb.2017.08.001","volume":"200","author":"B Wang","year":"2017","unstructured":"Wang B, Yin Q. AIM2 inflammasome activation and regulation: a structural perspective. J Struct Biol. 2017;200:279\u201382.","journal-title":"J Struct Biol"},{"key":"4726_CR18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28:27\u201330.","journal-title":"Nucleic Acids Res"},{"key":"4726_CR19","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 2019;28:1947\u201351.","journal-title":"Protein Sci"},{"key":"4726_CR20","doi-asserted-by":"publisher","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","volume":"49","author":"M Kanehisa","year":"2021","unstructured":"Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M. KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021;49:D545\u201351.","journal-title":"Nucleic Acids Res"},{"key":"4726_CR21","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.3390\/ijms18122618","volume":"18","author":"L Dib","year":"2017","unstructured":"Dib L, San-Jose LM, Ducrest AL, Salamin N, Roulin A. Selection on the major color gene melanocortin-1-receptor shaped the evolution of the melanocortin system genes. Int J Mol Sci. 2017;18:2618.","journal-title":"Int J Mol Sci"},{"key":"4726_CR22","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41420-021-00451-x","volume":"7","author":"Y Ye","year":"2021","unstructured":"Ye Y, Dai Q, Qi H. A novel defined pyroptosis-related gene signature for predicting the prognosis of overian cancer. Cell Death Discov. 2021;7:71.","journal-title":"Cell Death Discov"},{"key":"4726_CR23","doi-asserted-by":"publisher","first-page":"106477","DOI":"10.1016\/j.intimp.2020.106477","volume":"83","author":"Q Wu","year":"2020","unstructured":"Wu Q, Wang L, Wei H, Li B, Yang J, Wang Z, et al. Integration of multiple key molecules in lung adenocarcinoma identifies prognostic and immunotherapeutic relevant gene signatures. Int Immunopharmacol. 2020;83:106477.","journal-title":"Int Immunopharmacol"},{"key":"4726_CR24","doi-asserted-by":"publisher","first-page":"251","DOI":"10.4103\/0019-5154.182416","volume":"61","author":"A Hazra","year":"2016","unstructured":"Hazra A, Gogtay N. Biostatistics series module 3: comparing groups: numerical variables. Indian J Dermatol. 2016;61:251\u201360.","journal-title":"Indian J Dermatol"},{"key":"4726_CR25","doi-asserted-by":"publisher","first-page":"84658","DOI":"10.18632\/oncotarget.12384","volume":"7","author":"Q Chu","year":"2016","unstructured":"Chu Q, Jiang Y, Zhang W, Xu C, Du W, Gulnara T, et al. Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma. Oncotarget. 2016;7:84658\u201365.","journal-title":"Oncotarget"},{"key":"4726_CR26","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.canlet.2019.07.015","volume":"462","author":"Y Xiao","year":"2019","unstructured":"Xiao Y, Zhang H, Ma Q, Huang R, Lu J, Liang X, et al. YAP1-mediated pancreatic stellate cell activation inhibits pancreatic cancer cell proliferation. Cancer Lett. 2019;462:51\u201360.","journal-title":"Cancer Lett"},{"key":"4726_CR27","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.gtc.2017.01.001","volume":"46","author":"JH Chen","year":"2017","unstructured":"Chen JH, Deshpande V. IgG4-related disease and the liver. Gastroenterol Clin N Am. 2017;46:195\u2013216.","journal-title":"Gastroenterol Clin N Am"},{"key":"4726_CR28","doi-asserted-by":"publisher","first-page":"3136","DOI":"10.3748\/wjg.v25.i25.3136","volume":"25","author":"D Neureiter","year":"2019","unstructured":"Neureiter D, Stintzing S, Kiesslich T, Ocker M. Hepatocellular carcinoma: therapeutic advances in signaling, epigenetic and immune targets. World J Gastroenterol. 2019;25:3136\u201350.","journal-title":"World J Gastroenterol"},{"issue":"1217\u201330","key":"4726_CR29","first-page":"e17","volume":"173","author":"FFS Ke","year":"2018","unstructured":"Ke FFS, Vanyai HK, Cowan AD, Delbridge ARD, Whitehead L, Grabow S, et al. Embryogenesis and adult life in the absence of intrinsic apoptosis effectors BAX, BAK, and BOK. Cell. 2018;173(1217\u201330):e17.","journal-title":"Cell"},{"key":"4726_CR30","doi-asserted-by":"publisher","first-page":"426","DOI":"10.3390\/ijms22010426","volume":"22","author":"K Tsuchiya","year":"2021","unstructured":"Tsuchiya K. Switching from apoptosis to pyroptosis: gasdermin-elicited inflammation and antitumor immunity. Int J Mol Sci. 2021;22:426.","journal-title":"Int J Mol Sci"},{"key":"4726_CR31","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/s41564-020-0773-2","volume":"5","author":"P Deo","year":"2020","unstructured":"Deo P, Chow SH, Han ML, Speir M, Huang C, Schittenhelm RB, et al. Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation. Nat Microbiol. 2020;5:1418\u201327.","journal-title":"Nat Microbiol"},{"key":"4726_CR32","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1126\/science.aar7607","volume":"362","author":"S Ruhl","year":"2018","unstructured":"Ruhl S, Shkarina K, Demarco B, Heilig R, Santos JC, Broz P. ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation. Science. 2018;362:956\u201360.","journal-title":"Science"},{"key":"4726_CR33","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.4103\/1673-5374.300453","volume":"16","author":"LL Tan","year":"2021","unstructured":"Tan LL, Jiang XL, Xu LX, Li G, Feng CX, Ding X, et al. TP53-induced glycolysis and apoptosis regulator alleviates hypoxia\/ischemia-induced microglial pyroptosis and ischemic brain damage. Neural Regen Res. 2021;16:1037\u201343.","journal-title":"Neural Regen Res"},{"issue":"97\u2013108","key":"4726_CR34","first-page":"e4","volume":"24","author":"R Kang","year":"2018","unstructured":"Kang R, Zeng L, Zhu S, Xie Y, Liu J, Wen Q, et al. Lipid peroxidation drives gasdermin d-mediated pyroptosis in lethal polymicrobial sepsis. Cell Host Microbe. 2018;24(97\u2013108):e4.","journal-title":"Cell Host Microbe"},{"key":"4726_CR35","doi-asserted-by":"publisher","first-page":"2540","DOI":"10.4081\/ejh.2015.2540","volume":"59","author":"E Guerriero","year":"2015","unstructured":"Guerriero E, Capone F, Accardo M, Sorice A, Costantini M, Colonna G, et al. GPX4 and GPX7 over-expression in human hepatocellular carcinoma tissues. Eur J Histochem. 2015;59:2540.","journal-title":"Eur J Histochem"},{"key":"4726_CR36","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1002\/cbin.11444","volume":"44","author":"Q Xu","year":"2020","unstructured":"Xu Q, Zhou L, Yang G, Meng F, Wan Y, Wang L, et al. CircIL4R facilitates the tumorigenesis and inhibits ferroptosis in hepatocellular carcinoma by regulating the miR-541-3p\/GPX4 axis. Cell Biol Int. 2020;44:2344\u201356.","journal-title":"Cell Biol Int"},{"key":"4726_CR37","doi-asserted-by":"publisher","first-page":"3717","DOI":"10.1158\/1078-0432.CCR-17-3509","volume":"24","author":"T David","year":"2018","unstructured":"David T, Carlota RP, Ferran M, Radhakrishnan S, Josep MP, Aura M, et al. A Pan-cancer Landscape of Interactions between Solid Tumors and Infiltrating Immune Cell Populations. Clin Cancer Res. 2018;24:3717\u201328.","journal-title":"Clin Cancer Res"},{"issue":"338\u201354","key":"4726_CR38","first-page":"e15","volume":"173","author":"TM Malta","year":"2018","unstructured":"Malta TM, Sokolov A, Gentles AJ, Burzykowski T, Poisson L, Weinstein JN, et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell. 2018;173(338\u201354):e15.","journal-title":"Cell"},{"key":"4726_CR39","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1080\/21645515.2016.1199310","volume":"12","author":"G Kwok","year":"2016","unstructured":"Kwok G, Yau TC, Chiu JW, Tse E, Kwong YL. Pembrolizumab (Keytruda). Hum Vaccin Immunother. 2016;12:2777\u201389.","journal-title":"Hum Vaccin Immunother"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-022-04726-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-022-04726-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-022-04726-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T08:04:57Z","timestamp":1652429097000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-022-04726-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,13]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["4726"],"URL":"https:\/\/doi.org\/10.1186\/s12859-022-04726-7","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,13]]},"assertion":[{"value":"18 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"177"}}