To explore the effect of cytosolic phospholipase A2α (cPLA2α) on hepatocellular carcinoma (HCC) cell adhesion and the underlying mechanisms.

Cell adhesion, detachment, and hanging-drop assays were utilized to examine the effect of cPLA2α on the cell-matrix and cell-cell adhesion. Downstream substrates and effectors of cPLA2α were screened via a phospho-antibody microarray. Associated signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated via immunofluorescence. Western blot and immunohistochemistry were used to detect protein expression in HCC tissues. Prognosis evaluation was conducted using Kaplan-Meier and Cox-proportional hazards regression analyses.

Our findings showed that cPLA2α knockdown decreases cell-matrix adhesion but increases cell-cell adhesion in HepG2 cells. Microarray analysis revealed that phosphorylation of multiple proteins at specific sites were regulated by cPLA2α. These phosphorylated proteins were involved in various biological processes. In addition, our results indicated that the focal adhesion pathway was highly enriched in the cPLA2α-relevant signaling pathway. Furthermore, cPLA2α was found to elevate phosphorylation levels of FAK and paxillin, two crucial components of focal adhesion. Moreover, localization of p-FAK to focal adhesions in the plasma membrane was significantly reduced with the downregulation of cPLA2α. Clinically, cPLA2α expression was positively correlated with p-FAK levels. Additionally, high expression of both cPLA2α and p-FAK predicted the worst prognoses for HCC patients.

Our study indicated that cPLA2α may promote cell-matrix adhesion via the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC.

The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma (HB) in our single center and to evaluate periostin (POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was discussed.

POSTN expression was investigated in HB tumors by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB). The association among POSTN expression, clinicopathological features and overall survival (OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays, respectively. Epithelial-mesenchymal transition (EMT)-associated markers and activation of the ERK pathway were detected by WB.

HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated markers.

POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and invasion. Our study also suggests that POSTN may serve as a therapeutic biomarker in HB patients.

Hepatocellular carcinoma (HCC) is a lethal global disease that requires an accurate diagnosis. We assessed the potential of 5 serum biomarkers (AFP, AFU, GGT-II, GPC3, and HGF) in the diagnosis of HCC.

In this retrospective study, we measured the serum levels of each biomarker using ELISAs in 921 participants, including 298 patients with HCC, 154 patients with chronic hepatitis (CH), 122 patients with liver cirrhosis (LC), and 347 healthy controls from 3 hospitals. Patients negative for hepatitis B surface antigen and hepatitis C antibody (called “NBNC-HCC”) and patients positive for the above indices (called “HBV-HCC and HCV-HCC”) were enrolled. The selected diagnostic model was constructed using a training cohort (n = 468), and a validation cohort (n = 453) was used to validate our results. Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy.

The α-L-fucosidase (AFU)/α-fetoprotein (AFP) combination was best able to distinguish NBNC-HCC [area under the curve: 0.986 (95% confidence interval: 0.958–0.997), sensitivity: 92.6%, specificity: 98.9%] from healthy controls in the test cohort. For screening populations at risk of developing HCC (CH and LC), the AFP/AFU combination improved the diagnostic specificity for early-stage HCC [area under the curve: 0.776 (0.712–0.831), sensitivity: 52.5%, specificity: 91.6% in the test group]. In all-stage HBV-HCC and HCV-HCC, AFU was also the best candidate biomarker combined with AFP [area under the curve: 0.835 (0.784–0.877), sensitivity 69.1%, specificity: 87.4% in the test group]. All results were verified in the validation group.

The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.