{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:05:21Z","timestamp":1780445121784,"version":"3.54.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":52,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82273063"],"award-info":[{"award-number":["82273063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-45769-7","type":"journal-article","created":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:33:44Z","timestamp":1775986424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinicopathological significance of Gli1 expression in hepatocellular carcinoma: a meta-analysis"],"prefix":"10.1038","volume":"16","author":[{"given":"Sisi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"45769_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74, 229\u2013263 (2024).","journal-title":"CA Cancer J. Clin."},{"key":"45769_CR2","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1053\/j.gastro.2023.01.033","volume":"164","author":"MR Toh","year":"2023","unstructured":"Toh, M. R. et al. Global Epidemiology and Genetics of Hepatocellular Carcinoma. Gastroenterology 164, 766\u2013782 (2023).","journal-title":"Gastroenterology"},{"key":"45769_CR3","first-page":"108","volume":"161","author":"H Rumgay","year":"2022","unstructured":"Rumgay, H. et al. Global, regional and national burden of primary liver cancer by subtype. Eur. J. Cancer Oxf. Engl. 1990. 161, 108\u2013118 (2022).","journal-title":"Eur. J. Cancer Oxf. Engl. 1990"},{"key":"45769_CR4","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1053\/j.gastro.2018.08.065","volume":"156","author":"L Kulik","year":"2019","unstructured":"Kulik, L. & El-Serag, H. B. Epidemiology and Management of Hepatocellular Carcinoma. Gastroenterology 156, 477\u2013491e1 (2019).","journal-title":"Gastroenterology"},{"key":"45769_CR5","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/s41571-023-00825-3","volume":"20","author":"AG Singal","year":"2023","unstructured":"Singal, A. G., Kanwal, F. & Llovet, J. M. Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy. Nat. Rev. Clin. Oncol. 20, 864\u2013884 (2023).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"45769_CR6","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1002\/cam4.4551","volume":"11","author":"Y Liu","year":"2022","unstructured":"Liu, Y. et al. Global burden of primary liver cancer by five etiologies and global prediction by 2035 based on global burden of disease study 2019. Cancer Med. 11, 1310\u20131323 (2022).","journal-title":"Cancer Med."},{"key":"45769_CR7","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/s43018-022-00357-2","volume":"3","author":"JM Llovet","year":"2022","unstructured":"Llovet, J. M. et al. Molecular pathogenesis and systemic therapies for hepatocellular carcinoma. Nat. Cancer. 3, 386\u2013401 (2022).","journal-title":"Nat. Cancer"},{"key":"45769_CR8","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1002\/hep4.1564","volume":"4","author":"G Brar","year":"2020","unstructured":"Brar, G. et al. Hepatocellular Carcinoma Survival by Etiology: A SEER-Medicare Database Analysis. Hepatol. Commun. 4, 1541\u20131551 (2020).","journal-title":"Hepatol. Commun."},{"key":"45769_CR9","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nature03100","volume":"432","author":"PA Beachy","year":"2004","unstructured":"Beachy, P. A., Karhadkar, S. S. & Berman, D. M. Tissue repair and stem cell renewal in carcinogenesis. Nature 432, 324\u2013331 (2004).","journal-title":"Nature"},{"key":"45769_CR10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.semcancer.2021.04.003","volume":"85","author":"J Jiang","year":"2022","unstructured":"Jiang, J. Hedgehog signaling mechanism and role in cancer. Semin Cancer Biol. 85, 107\u2013122 (2022).","journal-title":"Semin Cancer Biol."},{"key":"45769_CR11","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1002\/hep.22649","volume":"49","author":"M Eichenm\u00fcller","year":"2009","unstructured":"Eichenm\u00fcller, M. et al. Blocking the hedgehog pathway inhibits hepatoblastoma growth. Hepatol. Baltim. Md. 49, 482\u2013490 (2009).","journal-title":"Hepatol. Baltim. Md."},{"key":"45769_CR12","doi-asserted-by":"crossref","unstructured":"Giammona, A., Crivaro, E. & Stecca, B. Emerging roles of hedgehog signaling in cancer immunity. Int. J. Mol. Sci. 24, (2023).","DOI":"10.3390\/ijms24021321"},{"key":"45769_CR13","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.3389\/fphar.2019.01039","volume":"10","author":"CY Zhang","year":"2019","unstructured":"Zhang, C. Y. et al. Saikosaponin-d Inhibits the Hepatoma Cells and Enhances Chemosensitivity Through SENP5-Dependent Inhibition of Gli1 SUMOylation Under Hypoxia. Front. Pharmacol. 10, 1039 (2019).","journal-title":"Front. Pharmacol."},{"key":"45769_CR14","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s12079-021-00645-z","volume":"16","author":"X Yu","year":"2022","unstructured":"Yu, X. et al. Hepatitis B virus x gene-downregulated growth-arrest specific 5 inhibits the cell viability and invasion of hepatocellular carcinoma cell lines by activating Y-box-binding protein 1\/p21 signaling. J. Cell. Commun. Signal. 16, 179\u2013190 (2022).","journal-title":"J. Cell. Commun. Signal."},{"key":"45769_CR15","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1093\/carcin\/bgi378","volume":"27","author":"S Huang","year":"2006","unstructured":"Huang, S. et al. Activation of the hedgehog pathway in human hepatocellular carcinomas. Carcinogenesis 27, 1334\u20131340 (2006).","journal-title":"Carcinogenesis"},{"key":"45769_CR16","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1038\/nm.3389","volume":"19","author":"D Amakye","year":"2013","unstructured":"Amakye, D., Jagani, Z. & Dorsch, M. Unraveling the therapeutic potential of the Hedgehog pathway in cancer. Nat. Med. 19, 1410\u20131422 (2013).","journal-title":"Nat. Med."},{"key":"45769_CR17","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1038\/s41467-018-05220-6","volume":"9","author":"AS Cazet","year":"2018","unstructured":"Cazet, A. S. et al. Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat. Commun. 9, 2897 (2018).","journal-title":"Nat. Commun."},{"key":"45769_CR18","doi-asserted-by":"crossref","unstructured":"Sigafoos, A. N., Paradise, B. D. & Fernandez-Zapico, M. E. Hedgehog\/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease. Cancers 13, (2021).","DOI":"10.3390\/cancers13143410"},{"key":"45769_CR19","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3233\/CBM-150542","volume":"16","author":"Y Wang","year":"2016","unstructured":"Wang, Y., Peng, Q., Jia, H. & Du, X. Prognostic value of hedgehog signaling pathway in digestive system cancers: A systematic review and meta-analysis. Cancer Biomark. Sect. Dis. Markers. 16, 71\u201379 (2016).","journal-title":"Cancer Biomark. Sect. Dis. Markers"},{"key":"45769_CR20","doi-asserted-by":"publisher","first-page":"22184","DOI":"10.1038\/srep22184","volume":"6","author":"J Cheng","year":"2016","unstructured":"Cheng, J., Gao, J. & Tao, K. Prognostic role of Gli1 expression in solid malignancies: a meta-analysis. Sci. Rep. 6, 22184 (2016).","journal-title":"Sci. Rep."},{"key":"45769_CR21","doi-asserted-by":"publisher","first-page":"113928","DOI":"10.1016\/j.celrep.2024.113928","volume":"43","author":"D Fan","year":"2024","unstructured":"Fan, D., Cong, Y., Liu, J., Zhang, H. & Du, Z. Spatiotemporal analysis of mRNA-protein relationships enhances transcriptome-based developmental inference. Cell. Rep. 43, 113928 (2024).","journal-title":"Cell. Rep."},{"key":"45769_CR22","unstructured":"Liu, J. B. & Tu, Z. G. Role of the nuclear transcription factor Gli1 in the SHH signaling pathway in hepatocellular carcinoma. (Chongqing: Chongqing Medical University). https:\/\/dwanfangdatacomcn\/thesis\/CiBUaGVzaXNOZXdTMjAyNTA2MTMyMDI1MDYxMzE2MTkxNhIIWTE1NDcxODgaCHo0MmRreHZy. (2009)."},{"key":"45769_CR23","unstructured":"Wang, H. C. A preliminary study on Hedgehog signaling pathway Gli1 gene and EMT-related factor MMP11 in hepatocellular carcinoma. (Taian: Taishan Medical University). https:\/\/dwanfangdatacomcn\/thesis\/CiBUaGVzaXNOZXdTMjAyNTA2MTMyMDI1MDYxMzE2MTkxNhIJRDAyMDIzMTA2GghyY2V1ajcyaQ%3D%3D.  (2018)."},{"key":"45769_CR24","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41392-023-01559-5","volume":"8","author":"J Jing","year":"2023","unstructured":"Jing, J. et al. Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies. Signal. Transduct. Target. Ther. 8, 315 (2023).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"45769_CR25","doi-asserted-by":"publisher","first-page":"3720","DOI":"10.1093\/eurheartj\/ehad191","volume":"44","author":"RA Byrne","year":"2023","unstructured":"Byrne, R. A. et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur. Heart J. 44, 3720\u20133826 (2023).","journal-title":"Eur. Heart J."},{"key":"45769_CR26","doi-asserted-by":"publisher","first-page":"509","DOI":"10.3350\/cmh.2024.0545","volume":"31","author":"JS Kim","year":"2025","unstructured":"Kim, J. S. et al. Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity. Clin. Mol. Hepatol. 31, 509\u2013524 (2025).","journal-title":"Clin. Mol. Hepatol."},{"key":"45769_CR27","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372, n71 (2021).","journal-title":"BMJ"},{"key":"45769_CR28","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","volume":"336","author":"GH Guyatt","year":"2008","unstructured":"Guyatt, G. H. et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336, 924\u2013926 (2008).","journal-title":"BMJ"},{"key":"45769_CR29","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.arcmed.2010.06.003","volume":"41","author":"XL Chen","year":"2010","unstructured":"Chen, X. L. et al. Chen J. Expression of sonic hedgehog signaling components in hepatocellular carcinoma and cyclopamine-induced apoptosis through Bcl-2 downregulation in vitro. Arch. Med. Res. 41, 315\u2013323 (2010).","journal-title":"Arch. Med. Res."},{"key":"45769_CR30","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/aps.2012.24","volume":"33","author":"J Lu","year":"2012","unstructured":"Lu, J., Zhao, W., He, W. & Wei, W. Lu Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway. Acta Pharmacol. Sin. 33, 691\u2013700 (2012).","journal-title":"Acta Pharmacol. Sin"},{"key":"45769_CR31","unstructured":"Yu, L. H., Yin, X. G., Yu, Y. W., Wu, W. X. & Zhang, Y. P. The role of Hedgehog signaling pathway effector proteins in hepatocellular carcinoma. Chin.  J. Hepatobiliary Surg. 19 198\u2013200. https:\/\/dwanfangdatacomcn\/periodical\/CiFQZXJpb2RpY2FsQ0hJU29scjlTMjAyNTEwMjEwOTUwNDYSD3poZ2R3azIwMTMwMzAwORoIejQyZGt4dnI%3D.  (2013)."},{"key":"45769_CR32","doi-asserted-by":"publisher","unstructured":"Ni, Z. R., Xie, K., Zhao, H. C., Zhu, L. X. & Geng, X. P. Clinical research on Shh, Gli1, Snail, and E-cadherin expression in hepatocellular carcinoma tissue. Acta Universitatis Medicinalis Anhui  536\u2013541. https:\/\/doi.org\/10.19405\/j.cnki.issn1000-1492.2016.04.017 (2016).","DOI":"10.19405\/j.cnki.issn1000-1492.2016.04.017"},{"key":"45769_CR33","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.3892\/ol.2016.4884","volume":"12","author":"HW Chun","year":"2016","unstructured":"Chun, H. W. & Hong, R. Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma. Oncol. Lett. 12, 1753\u20131762 (2016).","journal-title":"Oncol. Lett."},{"key":"45769_CR34","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.canlet.2016.02.053","volume":"375","author":"Q Li","year":"2016","unstructured":"Li, Q. et al. PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1. Cancer Lett. 375, 190\u2013198 (2016).","journal-title":"Cancer Lett."},{"key":"45769_CR35","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1620\/tjem.242.291","volume":"242","author":"N Nooron","year":"2017","unstructured":"Nooron, N., Ohba, K., Takeda, K., Shibahara, S. & Chiabchalard, A. Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma. Tohoku J. Exp. Med. 242, 291\u2013302 (2017).","journal-title":"Tohoku J. Exp. Med."},{"key":"45769_CR36","first-page":"2381","volume":"12","author":"B Chen","year":"2019","unstructured":"Chen, B. et al. The expressions of Hedgehog and PI3K-AKT pathway components correlate with invasion and metastasis in hepatocellular carcinoma. Int. J. Clin. Exp. Pathol. 12, 2381\u20132388 (2019).","journal-title":"Int. J. Clin. Exp. Pathol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45769-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45769-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45769-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T23:29:01Z","timestamp":1780442941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45769-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["45769"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-45769-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]},"assertion":[{"value":"10 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Ethical approval and patient consent were not required for this systematic review and meta-analysis, because they utilized only publicly available data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}],"article-number":"17065"}}