Fig. 1: Association of PGC7 expression with liver development and HCC oncogenic dedifferentiation.

a STEM (Short Time-series Expression Miner)-based trend analysis revealed two typical gene expression patterns in the model of in vitro hepatocyte differentiation. ES embryonic stem cell, EN endoderm, LP liver progenitor cell, PH premature hepatocytes, HEP average value of two cases of non-tumor tissues, HCC average value of two cases of tumor tissues. b PGC7 expression pattern was verified in the model of in vitro hepatocyte differentiation by qRT-PCR. Data were shown as the mean of three independent experiments. N1, N2, two cases of non-tumor specimens; T1, T2, two cases of HCC specimens. c PGC7 expression level was detected in 60 pairs of HCC samples by qRT-PCR. A paired t-test was used for statistical analysis. d PGC7 expression was detected in HCC clinical samples divided by tumor stage. Early-stage—stage1; advanced stage—stage 2 or 3; Student’s t-test was used for statistical analysis, **P < 0.01. e Expression levels of PGC7 were elevated in poor differentiated HCC (Poor diff) compared with well-differentiated HCC (Well diff) and non-tumor tissues by qRT-PCR. Student’s t-test was used for statistical analysis, *P < 0.05. f The association of PGC7 with CD133 (n = 61), CK19 (n = 36), AFP (n = 45), ALB (n = 46), and G6PC (n = 44) in HCC clinical specimens were detected by qRT-PCR. Pearson coefficient R was used to denote the expression correlation. g Representative IHC staining of PGC7 in non-tumor tissues and HCC clinical specimens. h Quantification of the PGC7 positive cells in Tumor and para-tumor tissues (upper left); Kaplan–Meier survival analysis showed HCC patients with PGC7 positive staining (n = 72) had worse survival outcome compared with patients without detectable PGC7 expression (n = 35) (upper right); Expression of PGC7 significantly associated with advanced tumor stage and relatively high AFP level (Fisher’s Exact Test, *P < 0.05, lower panel). i Percentage of PGC7 positive cells detected by FACS in immortalized liver and HCC cell lines. Data were shown as the mean of three independent experiments. j Representative dual-color immunofluorescence analysis of cryosectioned spheroids generated from PLC-8024 cells showing the colocalization of PGC7 (green) and CD133 (red). Three independent experiments were conducted.