Weber Florian, Utpatel Kirsten, Evert Katja, Weiss Thomas S, Buechler Christa
Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany.
Children's University Hospital (KUNO), Regensburg University Hospital, 93053 Regensburg, Germany.
Biomedicines. 2024 Oct 19;12(10):2397. doi: 10.3390/biomedicines12102397.
BACKGROUND/OBJECTIVES: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages.
Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients.
In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues.
In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging.
背景/目的：骨形态发生蛋白与激活素膜结合抑制剂（BAMBI）是转化生长因子（TGF）-β1信号通路的拮抗剂。BAMBI作为一种抗纤维化蛋白，具有促癌和抗癌活性。我们的研究旨在将肝细胞癌（HCC）中肝细胞BAMBI蛋白水平与T分期、淋巴结侵犯、血管侵犯、分级、肿瘤大小和国际癌症控制联盟（UICC）分期，以及与肝脏炎症和纤维化分期相关联。
通过免疫组织化学评估320例患者的HCC组织和51例患者的非肿瘤组织中肝细胞BAMBI蛋白表达。
在整个队列和性别特异性分析的HCC组织中，BAMBI蛋白与T分期、血管侵犯、淋巴结侵犯、组织学分级、UICC分期和肿瘤大小无关。因此，BAMBI与总生存期、无复发生存期和无转移生存期无关。肿瘤组织和非肿瘤组织中的BAMBI蛋白水平与炎症和纤维化分级无关。在一个小队列中通过免疫印迹分析以及在上述患者组织中通过免疫组织化学分析的HCC患者的HCC组织和非肿瘤组织中的BAMBI蛋白水平相似。值得注意的是，与疾病严重程度相当的乙型肝炎病毒（HBV）感染患者相比，丙型肝炎病毒（HCV）感染的HCC组织中BAMBI蛋白含量较低。免疫印迹分析显示，与HBV感染患者和正常肝组织相比，HCV感染患者的非肿瘤组织中BAMBI蛋白减少。
总之，该分析表明，HCC患者的肝细胞BAMBI蛋白水平与HCV感染有关，而与潜在肝病的严重程度和癌症分期无关。
