The correlation of fibrinogen-like protein-1 expression with the progression and prognosis of hepatocellular carcinoma

Abstract

Background Fibrinogen-like-protein 1 (FGL1), a member of the fibrinogen-related protein (FREP) family, is a major ligand of the immune inhibitory receptor lymphocyte-activation gene 3 (LAG-3). While FGL1 is strongly implicated in the development and prognosis of a variety of diseases, its role in hepatocellular carcinoma (HCC) is still disputed. Therefore, the role of FGL1 expression in the progression and prognosis of HCC was investigated. Methods and results In the present study, bioinformatics analysis was first used to probe the expression profile of FGL1 in multiple malignant tumor tissues and paired normal tissues, and to explore the possible relationship between FGL1 and prognosis of HCC patients. Thereafter, the expression levels of FGL1 were determined and compared in human HCC cell lines, HCC tissues, peri-tumor tissues and normal liver tissues by western blot analysis. Furthermore, tissue microarrays were used to detect the expression of FGL1 through immunohistochemical staining and to verify whether the FGL1 expression level was associated with clinicopathological features and the prognosis of HCC patients. The results showed that FGL1 was downregulated significantly in most of the HCC cells lines and HCC tissues, corresponding to the results of the bioinformatics and western blot analyses. FGL1 expression level in HCC was found to be correlated to Edmondson grade and metastasis of the HCC. Additionally, high FGL1 expression was associated with better overall survival in HCC patients, suggesting that FGL1 could function as a tumor suppressor. Conclusions The expression level of FGL1 can be correlated with the progression and prognosis of HCC, suggesting its potential as a prognostic biomarker.

Aspirin and immunotherapy: a Faustian bargain?

“…The results of Lin et al indicate that FGL1 expression is a negative prognosticator in HCC, as demonstrated by the association between FGL1 inhibition, antitumor immunity, and survival ( 4 ). Notably, these results contrast with prior findings in which downregulation of FGL1 in HCC increases the rates of tumor formation ( 15 – 17 ), and is a positive prognosticator ( 15 ). The discrepancy between the present study and others may be a function of analyzing the different ways in which FGL1 influences the development and progression of HCC.…”

Role of Fibrinogen-like Protein 1 in Tumor Recurrence Following Hepatectomy

“…Hence, FGL1 expression is linked to HCC progression and prognosis, supporting its use as a biomarker. 44 Another study investigated the association of the FGL1-LAG-3 pathway and programmed cell death ligand 1 (PD-L1) with prognosis in HCC. LAG-3, FGL1, PD-L1, and CD8 + T cells were measured in 143 HCC patients.…”

Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma

“…Moreover, FGL-1 expression within the tumor appeared to be correlated with the progression and prognosis of HCC, suggesting that FGL-1 could be used not only as a molecular target but also as a potential prognostic biomarker. 67 More research is needed in order to understand if LAG-3 through FGL-1 blockade could have a role as a new therapeutic strategy to overcome resistance to immunotherapy. In addition to its therapeutic role, it will be important to analyze the prognostic potential of FGL as a prognostic marker.…”