Ramakrishnan Krishnapriya, Sanjeev Diya, Rehman Niyas, Raju Rajesh
Centre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, India.
J Viral Hepat. 2025 Jan;32(1):e14035. doi: 10.1111/jvh.14035.
Alpha fetoprotein (AFP) is a glycoprotein of foetal origin belonging to the albumin protein family. Serum AFP is a long-conceived early-diagnostic biomarker for HCC with its elevated expression in different liver pathologies ranging from hepatitis viral infections to fibrosis, cirrhosis, and HCC. Beyond their utility as biomarkers, in support of its contribution to these clinical outcomes, the function of AFP as an immune suppressor and inducer of malignant transformation in HCC patients is well reported. Multiple reports show that AFP is secreted by hepatocytes, binds to its cognate receptor, AFP-receptor (AFPR), and exerts its actions. However, there is only limited information available in this context. There is an urgent need to gather more insight into the AFP signalling pathway and consider it a classical intracellular signalling pathway, among others. AFP is a highly potent intracellular molecule that has the potential to bind to many interactors like PTEN, Caspase, RAR, and so on. It has been shown that cellular AFP and secreted AFP have different roles in HCC pathophysiology, and a comprehensive map of the AFP signalling pathway is warranted for further theranostic applications.
甲胎蛋白(AFP)是一种源自胎儿的糖蛋白,属于白蛋白蛋白家族。血清AFP长期以来一直被视为肝癌的早期诊断生物标志物,在从病毒性肝炎感染到纤维化、肝硬化和肝癌等不同肝脏病变中其表达都会升高。除了作为生物标志物的用途外,为了支持其对这些临床结果的贡献,AFP作为肝癌患者免疫抑制剂和恶性转化诱导剂的功能已有充分报道。多项报告表明,AFP由肝细胞分泌,与其同源受体甲胎蛋白受体(AFPR)结合并发挥作用。然而,在这方面仅有有限的信息。迫切需要更深入地了解AFP信号通路,并将其视为经典的细胞内信号通路之一。AFP是一种高效的细胞内分子,有可能与许多相互作用分子如PTEN、半胱天冬酶、视黄酸受体等结合。研究表明,细胞内AFP和分泌型AFP在肝癌病理生理学中具有不同作用,因此有必要绘制一份全面的AFP信号通路图谱,以用于进一步的治疗诊断应用。