Abstract: Objective To guide the early diagnosis and treatment of hepatocellular carcinoma (HCC) through investigating the relationship between phosphatidylinositol proteoglycan 3 (GPC3) expression and malignant biological behavior of HCC.Methods The clinical data of 77 patients with HCC admitted to our hospital from December 2017 to August 2020 were retrospectively analyzed. All specimens were obtained from intraoperative pathologically resected tissues, HCC specimens were resected from the primary lesion, pericarcinomatous tissue was resected from the cancer adjacent liver tissues which was 5 cm away from the primary lesion, and normal liver tissue confirmed by pathology was resected from more than 5 cm away from the primary lesion. The GPC3 expression situations of different liver tissues were compared and the correlation between them and malignan biological behavior of HCC cells was analyzed [proliferation genes including: silent information regulator 6 (SIRT6), forkhead box P2 (FOXP2), hypoxia-inducible factor-1α (HIF-1α); hepatocyte apoptosis-related factors: phosphatidylinositol-3-kinase (PI3K), cysteine-containing aspartate protein hydrolase 3 (caspase-3), and serine threonine protein kinase (Akt)].Results The positive expression rates of GPC3 in HCC tissues, pericarcinomatous tissue normal tissues were 98.70% (76/77), 89.61% (69/77) and 2.60% (2/77) respectively, and the difference was statistically significant (χ²=275.074, P<0.001). The positive rate of GPC3 in normal liver tissues was significantly lower than that in pericarcinomatous tissue, (Z=10.421, P=0.004) and HCC tissues (Z=11.645, P<0.001). There was no significant difference of S100A2 expression grade among the different tissues (Z=6.839, P<0.001). Compared with pericarcinomatous tissue, the expression levels of GPC3, STC2, FOXP2, HIF-1α, SIRT6, PI3K, caspase-3 and Akt were higher in HCC tissues, the differences were statistically significant (P<0.05). Bivariate Pearson linear correlation test showed that GPC3 expressed in HCC tissues was positively associated with malignant biological behavior of cancer cells (proliferation genes: SIRT6, FOXP, HIF-1α; apoptosis-related factors: PI3K,caspase-3, Akt) (r>0, P<0.05).Conclusion There is a close relationship between GPC3 expression in HCC tissues and the biological behavior of cancer cells. GPC3 can be considered as a new target for HCC treatment, aimed at guiding the therapy of patients with HCC and improve prognosis.

Key words: Hepatocellular carcinoma, Phosphatidylinositol proteoglycan 3, Tumor, Biological behavior, Correlation