Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression
Abstract Hepatocellular cancer (HCC) therapy is in need for an ideal companion diagnostic. Preclinical experimental studies have identified the insulin receptor (IR) and its synergistic counterpart, the IGF1 receptor (IGF1R), as relevant in HCC development, and the ligands IGF1 and IGF2 have been fo...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85350-2 |
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| author | Steffen Markus Heckl Carolin Schneider Lukas Kercher Hans-Michael Behrens Jan-Paul Gundlach Alexander Bernsmeier Stephan Schmidt Sandra Krüger Felix Braun Rainer Günther Thomas Becker Stefan Schreiber Christoph Röcken |
| author_facet | Steffen Markus Heckl Carolin Schneider Lukas Kercher Hans-Michael Behrens Jan-Paul Gundlach Alexander Bernsmeier Stephan Schmidt Sandra Krüger Felix Braun Rainer Günther Thomas Becker Stefan Schreiber Christoph Röcken |
| author_sort | Steffen Markus Heckl |
| collection | DOAJ |
| description | Abstract Hepatocellular cancer (HCC) therapy is in need for an ideal companion diagnostic. Preclinical experimental studies have identified the insulin receptor (IR) and its synergistic counterpart, the IGF1 receptor (IGF1R), as relevant in HCC development, and the ligands IGF1 and IGF2 have been found to be elevated in HCC. This study aimed to bridge the gap to the clinical setting and explore whether the IR or the IGF1R would be of prognostic significance and would be associated with clinicopathologic parameters in HCC patients. In our retrospective cohort study located at the University Hospital Schleswig-Holstein, Campus Kiel, Germany, HCC samples of 139 patients were examined for IR and IGF1R expression by immunohistochemistry. A HistoScore was correlated with clinicopathological characteristics and survival. IR overexpression was frequently observed and was associated with clinicopathological parameters and survival. Membranous IR expression was associated with worse tumor specific survival (p = 0.043). Intriguingly, membranous IR expression was associated with worse tumor specific survival (p = 0.017) in the subgroup of patients undergoing sorafenib therapy. IGF1R expression was not associated with survival. In conclusion, our results suggest that membranous IR expression plays a role in HCC prognosis and treatment resistance, inspiring future validation as a potential companion diagnostic in HCC. |
| format | Article |
| id | doaj-art-3ba31bf3a2ff4c0582b6e3b0669da58b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-3ba31bf3a2ff4c0582b6e3b0669da58b2025-01-12T12:14:58ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-85350-2Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpressionSteffen Markus Heckl0Carolin Schneider1Lukas Kercher2Hans-Michael Behrens3Jan-Paul Gundlach4Alexander Bernsmeier5Stephan Schmidt6Sandra Krüger7Felix Braun8Rainer Günther9Thomas Becker10Stefan Schreiber11Christoph Röcken12Department of Pathology, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of Pathology, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of Pathology, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of Pathology, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of General, Visceral, Thoracic, Transplant and Pediatric Surgery, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of General, Visceral, Thoracic, Transplant and Pediatric Surgery, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of General, Visceral, Thoracic, Transplant and Pediatric Surgery, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of Pathology, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of General, Visceral, Thoracic, Transplant and Pediatric Surgery, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of Internal Medicine I, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of General, Visceral, Thoracic, Transplant and Pediatric Surgery, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of Internal Medicine I, Christian-Albrechts-University, University Hospital Schleswig-HolsteinDepartment of Pathology, Christian-Albrechts-University, University Hospital Schleswig-HolsteinAbstract Hepatocellular cancer (HCC) therapy is in need for an ideal companion diagnostic. Preclinical experimental studies have identified the insulin receptor (IR) and its synergistic counterpart, the IGF1 receptor (IGF1R), as relevant in HCC development, and the ligands IGF1 and IGF2 have been found to be elevated in HCC. This study aimed to bridge the gap to the clinical setting and explore whether the IR or the IGF1R would be of prognostic significance and would be associated with clinicopathologic parameters in HCC patients. In our retrospective cohort study located at the University Hospital Schleswig-Holstein, Campus Kiel, Germany, HCC samples of 139 patients were examined for IR and IGF1R expression by immunohistochemistry. A HistoScore was correlated with clinicopathological characteristics and survival. IR overexpression was frequently observed and was associated with clinicopathological parameters and survival. Membranous IR expression was associated with worse tumor specific survival (p = 0.043). Intriguingly, membranous IR expression was associated with worse tumor specific survival (p = 0.017) in the subgroup of patients undergoing sorafenib therapy. IGF1R expression was not associated with survival. In conclusion, our results suggest that membranous IR expression plays a role in HCC prognosis and treatment resistance, inspiring future validation as a potential companion diagnostic in HCC.https://doi.org/10.1038/s41598-025-85350-2Hepatocellular cancerIGF1 receptorInsulin receptorPrognosisSorafenib |
| spellingShingle | Steffen Markus Heckl Carolin Schneider Lukas Kercher Hans-Michael Behrens Jan-Paul Gundlach Alexander Bernsmeier Stephan Schmidt Sandra Krüger Felix Braun Rainer Günther Thomas Becker Stefan Schreiber Christoph Röcken Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression Scientific Reports Hepatocellular cancer IGF1 receptor Insulin receptor Prognosis Sorafenib |
| title | Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression |
| title_full | Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression |
| title_fullStr | Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression |
| title_full_unstemmed | Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression |
| title_short | Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression |
| title_sort | worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression |
| topic | Hepatocellular cancer IGF1 receptor Insulin receptor Prognosis Sorafenib |
| url | https://doi.org/10.1038/s41598-025-85350-2 |
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