Fig. 3
EV-SF3B4 expression and its diagnostic power in HCC. A Box plot of SF3B4 expression in blood-derived EVs from different diseases. NP, normal person; CHD, coronary heart disease; CRC, colorectal cancer; HCC, hepatocellular carcinoma; PAAD, pancreatic adenocarcinoma; WhB, whole blood; TPM, transcripts per million. B NTA of serum-derived EVs and Western blot analysis of EV and ER markers from serum EV and SNU449 cell lysates. C Gene expression of SF3B4 in MIHA and SNU449 cell lysates and derived EVs. D Representative immunofluorescence of endocytic and EV markers from MIHA cells treated with SNU449-derived EVs. E The expression of SF3B4 in MIHA cells treated with SNU449-derived EVs. F Effect of the inhibitor of clathrin-dependent endocytosis on decreasing SF3B4 expression. G SF3B4 mRNA expression comparison between healthy controls and patients with HCC in the buffy coat RNA (left), serum RNA (middle), and serum EV-RNA (right). H Expression of serum EV-SF3B4 based on the stage of liver disease in cohort 3. Statistically significant differences were determined using one-way ANOVA with Tukey’s multiple comparisons test. Compared to HC; ***P <0.001, compared to CH; ##P <0.01, ###P <0.001, compared to LC; §§§P <0.001. I Expression of serum EV-SF3B4 based on the stage of liver disease in the external cohort. Statistically significant differences were determined using one-way ANOVA with Tukey’s multiple comparisons test. Compared to HC; ***P <0.001, compared to CH; ###P <0.001, compared to LC; §§§P <0.001. J AUCs of serum EV-SF3B4 compared to serum AFP for diagnosing HCC in cohort 3. From left to right: diagnose all stages of HCC, mUICC stage I or II, and mUICC stage I. K AUCs of serum EV-SF3B4 for diagnosing HCC in the CH, LC, and HCC subgroups, compared to those of AFP in cohort 3. From left to right: diagnose all stages of HCC, mUICC stage I or II, and mUICC stage I. L AUCs of serum EV-SF3B4 compared to serum AFP for diagnosing HCC in the external cohort. From left to right: diagnose all stages of HCC, mUICC stage I or II, and mUICC stage I. M AUCs of serum EV-SF3B4 for diagnosing HCC in the CH, LC, and HCC subgroups compared to those of AFP in the external cohort. From left to right: diagnose all stages of HCC, mUICC stage I or II, and mUICC stage I