Fig 1: CECs enumeration in blood in patients with liver cirrhosis or HCC. CECs are characterized by either double staining (CK+/ASGR1+) or single staining (CK+/ASGR1-) in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients (A). The latter are divided into early (eHCC) and advanced (aHCC) disease for both, double (B) and single staining (C). p values for Kruskal Wallis test and multiple comparisons are:**p = 0.0096 and *p = 0.035 (A) and **p = 0.0051 (C).
Fig 2: Relationship between CEC characterization and clinical and pathological features in patients with liver cirrhosis or HCC. (A) Shows AFP levels divided by high (>400 ng/ml) and low (<400 ng/ml) for three groups of patients: LC = liver cirrhosis; HCC of cirrhosis etiology and HCC of other a etiology. (B) Shows frequency distribution of CECs for the same groups of patients. (C,D) Represent percentages of CECs with lack of ASGR1 expression for either the three previous group of patients (C) or Child-Pugh scores (D). p values for Chi-Square tests are shown for graphs (A,B). No significant differences are shown in C and D for Kruskal Wallis tests.
Fig 3: Risk factors for HCC. (A) Shows presence/absence of CECs and (B) shows number of CECs expressing (or not) ASGR1 in liver cirrhosis (LC) or hepatocellular carcinoma patients (HCC). (C,D) show same information as in (A,B) respectively, but dividing HCC individuals by either early (eHCC) or advanced (aHCC) disease stages.
Fig 4: Survival curves for patients with liver cirrhosis or HCC accounting for CEC numbers and phenotype. Left part of the figure represents overall survival curves for the whole population (A), only for those positive for CECs (B) and for those negative for CECs (C). Colors are Grey = eHCC and Black: aHCC. Right part of the figure represents progression-free survival for patients with all CECs positive for ASGR1 (D), patients with all CECs negative for ASGR1 (E) and patients with heterogeneous CEC phenotypes (F). Colors are: Dotted Grey = liver cirrhosis; Grey eHCC and Black: aHCC.
Fig 5: CECs heterogeneity in patients with liver cirrhosis or HCC. Heterogeneity is shown with respect to Cytokeratin (CK) and ASGR1 expression in two LC (liver cirrhosis) patients (top), two eHCC (early HCC) patients (middle) and two aHCC (advanced HCC) patients (bottom). In each case, one CEC positive for the two markers (CK and ASGR1) and one CEC negative for ASGR1 are shown. Hoechst is used as nuclear staining.
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