Background Fibrinogen-like protein 1 (FGL1)—Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown. Methods The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8 + T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker’s expression and clinical significances were studied. Results We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3 + cells but not PD-L1. CD8 + T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3 + cells and low levels of CD8 + T cells were correlated with poor disease outcome. Moreover, LAG-3 + cells deteriorated patient stratification based on the abundance of CD8 + T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC + ) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC − ). Furthermore, PD-L1 TC − in combination with high densities of LAG-3 + cells showed the worst prognosis, and PD-L1 TC + patients with low densities of LAG-3 + cells had the best prognosis. Conclusions LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3 + cells and CD8 + T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.
Background: fibrinogen-like protein 1 (FGL1) - Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown.Methods: The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8+T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker’s expression and clinical significances were studied.Results: We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3+cells but not PD-L1. CD8+ T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3+cells and low levels of CD8+ T cells were correlated with poor disease outcome. Moreover, LAG-3+cells deteriorated patient stratification based on the abundance of CD8+ T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC+) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC-). Furthermore, PD-L1 TC- in combination with high densities of LAG-3+cells showed the worst prognosis, and PD-L1 TC+ patients with low densities of LAG-3+cells had the best prognosis.Conclusions: LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3+cells and CD8+ T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.
The objective of our study was to investigate the epidemiologic characteristics, prognostic factors and survival in patients with primary hepatic lymphoma (PHL).Methods: PHL patients diagnosed between 1983 and 2015 were identified from the SEER database. The temporal trend in PHL incidence was assessed using joinpoint regression software. Overall survival(OS) and disease-specific survival (DSS) was evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors.Results: A total of 1,182 patients were identified with PHL. The mean age was 61.7 ± 17.1 years with a male to female of 1.6:1. Diffuse large B-cell lymphoma (59.8%) was the most common histological subtype. The incidence of PHL steadily increasing by an annual percentage change (APC) of 2.6% (95% CI 2.0-3.2, P < 0.05). The 1-, 5-, and 10-year OS rates were 50.85, 39.6, and 30.4%, respectively, and the corresponding DSS rates were 55.3, 47.9, and 43.3%, respectively. Multivariate Cox regression analysis revealed that age, sex, race, marital status, histological subtype, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for DLBCL were constructed to predict 1-, 5-, and 10-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance.Conclusion: PHL were rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for DLBCL were robust and accurate in predicting 1-, 5-, and 10-year OS and DSS.
Systemic sclerosis (SSc) is an immune-mediated connective tissue disease characterized by fibrosis of multi-organs, and SSc-related interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality. To explore molecular biological mechanisms of SSc-ILD, we constructed a competing endogenous RNA (ceRNA) network for prediction. Expression profiling data were obtained from the Gene Expression Omnibus (GEO) database, and differential expressed mRNAs and miRNAs analysis was further conducted between normal lung tissue and SSc lung tissue. Also, the interactions of miRNA–lncRNA, miRNA–mRNA, and lncRNA–mRNA were predicted by online databases including starBase, LncBase, miRTarBase, and LncACTdb. The ceRNA network containing 11 lncRNAs, 7 miRNAs, and 20 mRNAs were constructed. Based on hub genes and miRNAs identified by weighted correlation network analysis (WGCNA) method, three core sub-networks—SNHG16, LIN01128, RP11-834C11.4(LINC02381)/hsa-let-7f-5p/IL6, LINC01128/has-miR-21-5p/PTX3, and LINC00665/hsa-miR-155-5p/PLS1—were obtained. Combined with previous studies and enrichment analyses, the lncRNA-mediated network affected LPS-induced inflammatory and immune processes, fibrosis development, and tumor microenvironment variations. The ceRNA network, especially three core sub-networks, may be served as early biomarkers and potential targets for SSc, which also provides further insights into the occurrence, progression, and accurate treatment of SSc at the molecular level.
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BackgroundTransarterial chemoembolization (TACE) stands for the most commonly utilized therapy for hepatocellular carcinoma (HCC) worldwide. This study was to explore the potential predictive and prognostic roles of LAG-3 and PD-L1 as serum biomarkers in HCC patients underwent TACE treatment.MethodsA total of 100 HCC patients receiving TACE as well as 30 healthy controls were enrolled in the study. Serum LAG-3 and PD-L1 levels were determined at baseline and 3 day after TACE using enzyme-linked immunosorbent assay (ELISA).ResultsWe found serum levels of LAG-3 and PD-L1 were significantly elevated in HCC patients compared with healthy controls. Interestingly, patients with low pre-TACE and post-TACE levels of LAG-3 but not PD-L1 had a high probability of achieving an objective response (OR) after TACE treatment. Additionally, high pre-TACE LAG-3 level was correlated with poor disease outcome, and the patients with both high serum LAG-3 and PD-L1 level had the shorter overall survival (OS) than patients who are either PD-L1 or LAG-3 high or both PD-L1 and LAG-3 low. High pre-TACE serum LAG-3 level was positively associated with more cirrhosis pattern, advanced BCLC stage, pre-TACE alanine aminotransferase (ALT) level, and pre-TACE aspartate aminotransferase (AST) level. Furthermore, in 50 patients who underwent TACE, the serum LAG-3 level was significantly decreased at 3 day after TACE.ConclusionBoth pre-TACE and post-TACE serum LAG-3 levels could serve as powerful predictors for tumor response of TACE, and high pre-TACE serum LAG-3 level was an indicator for poor prognosis in HCC.
Background FGL1-LAG-3 pathway is a promising immunotherapeutic target and has synergistic effect with PD-1/PD-L1. However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unkonwn. Method The distributions, associations, and clinical significances of LAG-3, FGL1, PD-L1 and CD8 protein expression in 143 HCC patients were assessed by multiplex immunofluorescence. Results We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3 + cells but not PD-L1. CD8 + T cells densities had positive correlation with PD-L1 levels and negative asscociation with FGL1 expression. Elevated densities of LAG-3 + cells and low levels of CD8 + T cells were correlated with poor disease outcome.Moreover,LAG-3 + cells deteriorated patient stratification based on the abundance of CD8 + T cells. Paitents with positive PD-L1 expression on tumor cells (PD-L1TC + ) tended to have a improved survival than that with negative PD-L1 expression on tumor cells (PD-L1TC - ). Futhermore, PD-L1TC - in combination with high densities of LAG-3 + cells showed the worst prognosis, and PD-L1TC + patients with low densities of LAG-3 + cells had the best prognosis. Conclusions LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3 + cells and CD8 + T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively. Levels of LAG-3 + cells in combination with PD-L1 status on tumor cells have potential to identify patients who may benefit from immune checkpoints blockade combination strategies.
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