Leeming Diana Julie, Nielsen Signe Holm, Vongsuvanh Roslyn, Uchila Pruthviraj, Nielsen Mette Juul, Reese-Petersen Alexander L, van der Poorten David, Eslam Mohammed, Schuppan Detlef, Karsdal Morten Asser, George Jacob
Nordic Bioscience, Fibrosis Biology & Biomarkers, Herlev, Denmark.
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark.
Hepat Oncol. 2020 Dec 18;8(2):HEP32. doi: 10.2217/hep-2020-0030.
Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer types with a high amount of fibrosis activity, namely for outcome in hepatocellular carcinoma (HCC) cirrhotic patients.
PATIENTS & METHODS: Plasma C6M, PRO-C6 and alphafeto-protein (AFP) were assessed in 309 patients with mixed etiologies (hepatitis C, hepatitis B, alcohol and nonalcoholic fatty liver) diagnosed as cirrhotics, cirrhotics with HCC, noncirrhotics and healthy controls. Progression-free survival and overall survival (OS) data were collected up to 6120 days after diagnosis. The ability of each marker to predict survival was investigated.
RESULTS & CONCLUSION: The level of endotrophin assessed by PRO-C6 was able to separate healthy controls, noncirrhotics and cirrhotics from HCC (p < 0.05-0.0001). Both endotrophin and C6M provided value in the prediction of OS in cirrhotic patients with HCC. In the multivariate analysis for identifying HCC, in patients with high endotrophin (highest quartile) and that were positive for AFP (≥20 IU/ml), the hazard ratio for predicting OS was increased from 3.7 (p = 0.0006) to 14.4 (p = 0.0001) when comparing with AFP positive as a stand-alone marker. In conclusion, plasma levels for markers of Type VI collagen remodeling were associated with survival in cirrhotic patients with HCC. A combination of AFP with endotrophin improved the prognostic value compared with AFP alone for predicting OS in cirrhotic patients with HCC.
VI型胶原蛋白正逐渐成为一种源自不同类型成纤维细胞的信号胶原蛋白。VI型胶原蛋白的一个特定片段，即前肽，也被称为激素内营养蛋白。我们推测这种成纤维细胞激素在具有高纤维化活性的癌症类型中具有特殊意义，即对肝细胞癌（HCC）肝硬化患者的预后具有重要影响。
对309例病因混合（丙型肝炎、乙型肝炎、酒精性和非酒精性脂肪肝）的肝硬化患者、肝硬化合并HCC患者、非肝硬化患者和健康对照者进行血浆C6M、PRO-C6和甲胎蛋白（AFP）评估。收集诊断后长达6120天的无进展生存期和总生存期（OS）数据。研究了每个标志物预测生存的能力。
通过PRO-C6评估的内营养蛋白水平能够将健康对照者、非肝硬化患者和肝硬化患者与HCC患者区分开来（p<0.05 - 0.0001）。内营养蛋白和C6M在预测肝硬化合并HCC患者的OS方面均具有价值。在识别HCC的多变量分析中，对于内营养蛋白水平高（最高四分位数）且AFP阳性（≥20 IU/ml）的患者，与单独以AFP作为标志物相比，预测OS的风险比从3.7（p = 0.0006）增加到14.4（p = 0.0001）。总之，VI型胶原蛋白重塑标志物的血浆水平与肝硬化合并HCC患者的生存相关。与单独使用AFP相比，AFP与内营养蛋白联合使用可提高预测肝硬化合并HCC患者OS的预后价值。
