Hepatocellular carcinoma (HCC) is a common malignant tumor with a high morbidity and mortality in China and elsewhere in the world. Due to its tumor heterogeneity and distant metastasis, patients with HCC often have a poor prognosis. A surgical treatment such as a radical hepatectomy is still the treatment of choice for patients with HCC in current clinical practice. However, the high rate of recurrence and rate of metastasis after surgery diminishes the survival of and prognosis for these patients. In an era of targeted therapy and immunotherapy, the surgical treatment of HCC must change. This review focuses on the definition, feasibility, and criteria with which to evaluate neoadjuvant therapy for HCC in order to provide a new perspective on surgical treatment of HCC.

Decreased intercellular adhesion is a key step in the metastasis and recurrence of many cancers, including hepatocellular carcinoma (HCC). SVEP1 is an important cell adhesion molecule that plays a key role in regulating intercellular adhesion and embryonic lymphatic development. However, the expression patterns and roles of SVEP1 in HCC are still largely unknown. We identified SVEP1 expression by analyzing 220 HCC samples from our cancer center. TCGA and GEO online-databases were used for data calibration and validation. SVEP1 was differentially expressed in two groups of HCCs with different risks of recurrence and was deemed as an independent risk factor for the prognosis of HCC. The expression of SVEP1 is negatively related to the proliferation and metastasis of HCC. Downregulation of SVEP1 expression promoted in vitro HCC cell migration, chemotaxis, invasion and proliferation, as well as in vivo tumor growth, local invasion and metastasis in a mouse model. Bioinformatic analysis and RT-PCR results showed that miR-1269b expression is negatively correlated with the SVEP1 expression and the prognosis of HCC patients. Further experiments showed that miR-1269b directly targets and downregulates the expression of SVEP1, which further induces the phosphorylation of Akt at thr308. These regulatory effects ultimately mediate the proliferation and metastasis of HCC cells. SVEP1 could serve as a promising prognostic marker of HCC. MiR-1269b downregulates SVEP1 expression and promotes HCC proliferation and metastasis likely through the PI3k/Akt signaling pathway.

Some studies have reported that activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1 is a critical ribosome rarely reported in human tumors. This study aimed to explore the molecular mechanisms of PNO1 in HCC. Using 150 formalin-fixed and paraffin-embedded samples and 8 fresh samples, we found high PNO1 expression in HCC tumor tissues through Western blotting and RT-PCR. Moreover, the higher PNO1 expression was associated with poor HCC prognosis patients. In vitro and in vivo experiments indicated that PNO1 overexpression promoted the proliferation and depressed the apoptosis of HCC cells. High PNO1 expression also increased the autophagy of HCC cells. The molecular mechanisms underlying PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results showed that PNO1 promoted HCC progression through the MAPK signaling pathway. Therefore, PNO1 was overexpressed in HCC, promoted autophagy, and inhibited the apoptosis of HCC cells through the MAPK signaling pathway.

Many studies have shown that the hyperactivation of ribosome biogenesis plays essential roles in the initiation and progression of cancers. As a ribosome assembly factor, PNO1 plays an important role in ribosome biogenesis. However, little is known about the expression and function of PNO1 in human tumors. In our present study, we aimed to explore the functional roles and the underlying molecular mechanisms of PNO1 in human lung adenocarcinoma (LUAD). Both bioinformatics databases and tumor tissues demonstrated that the expression of PNO1 in LUAD tissues was higher than that in adjacent tissues and predicted poor survival in LUAD patients. In vitro and in vivo assays suggested that downregulation of PNO1 expression suppressed LUAD cell proliferation and invasion. Further studies found that miR-340-5p depressed PNO1 expression via direct binding to the 3′ untranslated region (UTR) of PNO1. PNO1 expression was negatively correlated with miR-340-5p expression in LUAD cells and tissue samples. Moreover, upregulation or downregulation of miR-340-5p expression reversed the effects of PNO1 inhibition and overexpression, respectively. Meanwhile, downregulation of PNO1 inhibited Notch signaling pathway which modulated epithelial mesenchymal transition (EMT). These results indicate that PNO1, negatively regulated by miR-340-5p, played an important role in LUAD progression via Notch signaling pathway. The miR-340-5p/PNO1/Notch axis might be a potential target for individualized and precise treatment of LUAD patients in the future.

Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial

Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds: A large-scale, retrospective study