Heckl Steffen Markus, Schneider Carolin, Kercher Lukas, Behrens Hans-Michael, Gundlach Jan-Paul, Bernsmeier Alexander, Schmidt Stephan, Krüger Sandra, Braun Felix, Günther Rainer, Becker Thomas, Schreiber Stefan, Röcken Christoph
Department of Pathology, Christian-Albrechts-University, University Hospital Schleswig-Holstein, 24105, Kiel, Germany.
Department of Internal Medicine II, Christian-Albrechts-University, University Hospital Schleswig-Holstein, 24105, Kiel, Germany.
Sci Rep. 2025 Jan 7;15(1):1209. doi: 10.1038/s41598-025-85350-2.
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.
肝细胞癌（HCC）治疗需要一种理想的伴随诊断方法。临床前实验研究已确定胰岛素受体（IR）及其协同对应物胰岛素样生长因子1受体（IGF1R）与HCC发展相关，并且已发现配体IGF1和IGF2在HCC中升高。本研究旨在弥合与临床环境之间的差距，并探讨IR或IGF1R是否具有预后意义以及是否与HCC患者的临床病理参数相关。在我们位于德国基尔大学医院石勒苏益格 - 荷尔斯泰因校区的回顾性队列研究中，通过免疫组织化学检查了139例患者的HCC样本中的IR和IGF1R表达。组织学评分与临床病理特征和生存率相关。经常观察到IR过表达，并且其与临床病理参数和生存率相关。膜性IR表达与较差的肿瘤特异性生存率相关（p = 0.043）。有趣的是，在接受索拉非尼治疗的患者亚组中，膜性IR表达与较差的肿瘤特异性生存率相关（p = 0.017）。IGF1R表达与生存率无关。总之，我们的结果表明膜性IR表达在HCC预后和治疗耐药中起作用，这为未来作为HCC潜在伴随诊断的验证提供了依据。
