Department of Pathology, Akdeniz University Medical School, Antalya 07070, Turkey.
World J Gastroenterol. 2021 Dec 7;27(45):7739-7747. doi: 10.3748/wjg.v27.i45.7739.
In this editorial, the roles of orosomucoid (ORM) in the diagnoses and follow-up assessments of both nonneoplastic diseases and liver tumors are discussed with respect to the publication by Zhu presented in the previous issue of (2020; 26(8): 840-817). ORM, or alpha-1 acid glycoprotein (AGP), is an acute-phase protein that constitutes 1% to 3% of plasma proteins in humans and is mainly synthesized in the liver. ORM exists in serum as two variants: ORM1 and ORM2. Although the variants share 89.6% sequence identity and have similar biological properties, ORM1 constitutes the main component of serum ORM. An interesting feature of ORM is that its biological effects differ according to variations in glycosylation patterns. This variable feature makes ORM an attractive target for diagnosing and monitoring many diseases, including those of the liver. Recent findings suggest that a sharp decrease in ORM level is an important marker for HBV-associated acute liver failure (ALF), and ORM1 plays an important role in liver regeneration. In viral hepatitis, increases in both ORM and its fucosylated forms and the correlation of these increases with fibrosis progression suggest that this glycoprotein can be used with other markers as a noninvasive method in the follow-up assessment of diseases. In addition, similar findings regarding the level of the asialylated form of ORM, called asialo-AGP (AsAGP), have been reported in a follow-up assessment of fibrosis in chronic liver disease. An increase in ORM in serum has also been shown to improve hepatocellular carcinoma (HCC) diagnosis performance when combined with other markers. In addition, determination of the ORM level has been useful in the diagnosis of HCC with AFP concentrations less than 500 ng/mL. For monitoring patients with AFP-negative HCC, a unique trifucosylated tetra-antennary glycan of ORM may also be used as a new potential marker. The fact that there are very few studies investigating the expression of this glycoprotein and its variants in liver tissues constitutes a potential limitation, especially in terms of revealing all the effects of ORM on carcinogenesis and tumor behavior. Current findings indicate that ORM2 expression is decreased in tumors, and this is related to the aggressive course of the disease. Parallel to this finding, in HCC cell lines, ORM2 decreases HCC cell migration and invasion, supporting reports of its tumor suppressor role. In conclusion, the levels of ORM and its different glycosylated variants are promising additional biomarkers for identifying ALF, for monitoring fibrosis in viral hepatitis, and for diagnosing early HCC. Although there is evidence that the loss of ORM2 expression in HCC is associated with poor prognosis, further studies are needed to support these findings. Additionally, investigations of ORM expression in borderline dysplastic nodules and hepatocellular adenomas, which pose diagnostic problems in the differential diagnosis of HCC, especially in biopsy samples, may shed light on whether ORM can be used in histopathological differential diagnosis.
在本期社论中，我们将讨论朱等人在之前一期 （2020 年；26(8)：840-817）中发表的文章中所讨论的粘蛋白（ORM）在非肿瘤性疾病和肝肿瘤的诊断和随访评估中的作用。ORM，或α-1酸性糖蛋白（AGP），是一种急性期蛋白，占人类血浆蛋白的 1%至 3%，主要在肝脏中合成。ORM 以两种变体形式存在于血清中：ORM1 和 ORM2。尽管变体共享 89.6%的序列同一性并且具有相似的生物学特性，但 ORM1 构成了血清 ORM 的主要成分。ORM 的一个有趣特征是，其生物学效应根据糖基化模式的变化而不同。这种可变特征使 ORM 成为诊断和监测许多疾病的有吸引力的靶标，包括肝脏疾病。最近的研究结果表明，ORM 水平的急剧下降是乙型肝炎病毒相关急性肝衰竭（ALF）的重要标志物，而 ORM1 在肝脏再生中发挥重要作用。在病毒性肝炎中，ORM 及其岩藻糖化形式的增加，以及这些增加与纤维化进展的相关性，表明该糖蛋白可以与其他标志物一起用作疾病随访评估的非侵入性方法。此外，在慢性肝病的纤维化随访评估中，也报道了 ORM 的无唾液酸形式（称为无唾液酸-AGP（AsAGP））水平的类似发现。血清中 ORM 的增加也已被证明在与其他标志物结合时可改善肝细胞癌（HCC）的诊断性能。此外，确定 ORM 水平对于 AFP 浓度低于 500ng/ml 的 HCC 的诊断也很有用。对于监测 AFP 阴性 HCC 的患者，ORM 的独特三岩藻糖基四天线糖基也可用作新的潜在标志物。研究人员很少研究这种糖蛋白及其变体在肝组织中的表达，这可能是一个潜在的局限性，尤其是在揭示 ORM 对癌变和肿瘤行为的所有影响方面。目前的研究结果表明，ORM2 在肿瘤中的表达减少，这与疾病的侵袭性过程有关。与此发现平行的是，在 HCC 细胞系中，ORM2 降低了 HCC 细胞的迁移和侵袭，支持其肿瘤抑制作用的报道。总之，ORM 及其不同糖基化变体的水平是识别 ALF、监测病毒性肝炎纤维化和诊断早期 HCC 的有前途的附加生物标志物。尽管有证据表明 HCC 中 ORM2 表达的丧失与预后不良有关，但需要进一步的研究来支持这些发现。此外，对边界性发育不良结节和肝细胞腺瘤（在 HCC 的鉴别诊断中，尤其是在活检样本中，这些病变存在诊断问题）中 ORM 的表达进行研究，可能有助于了解 ORM 是否可用于组织病理学鉴别诊断。
