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The aim of this study is to explore the prognostic value of vascular invasion (VI) in hepatocellular carcinoma (HCC) by searching for competing endogenous RNAs (ceRNA) network and constructing a new prognostic model for HCC. The differentially expressed genes (DEGs) between HCC and normal tissues were identified from GEO and TCGA. StarBase and miRanda prediction tools were applied to construct a circRNA-miRNA-mRNA network. The DEGs between HCC with and without VI were also identified. Then, the hub genes were screened to build a prognostic risk score model through the method of least absolute shrinkage and selection operator. The prognostic ability of the model was assessed using the Kaplan−Meier method and Cox regression analysis. In result, there were 221 up-regulated and 47 down-regulated differentially expressed circRNAs (DEcircRNAs) in HCC compared with normal tissue. A circRNA-related ceRNA network was established, containing 11 DEcircRNAs, 12 DEmiRNAs, and 161 DEmRNAs. Meanwhile, another DEG analysis revealed 625 up-regulated and 123 down-regulated DEGs between HCC with and without VI, and then a protein–protein interaction (PPI) network was built based on 122 VI-related DEGs. From the intersection of DEGs within the PPI and ceRNA networks, we obtained seven hub genes to build a novel prognostic risk score model. HCC patients with high-risk scores had shorter survival time and presented more advanced T/N/M stages as well as VI occurrence. In conclusion a novel prognostic model based on seven VI-associated DEGs within a circRNA-related ceRNA network was constructed in this study, with great ability to predict the outcome of HCC patients.

Immune checkpoint blockade (ICB) therapy is a promising treatment for hepatocellular carcinoma (HCC). However, it is limited by low response rates. Tumour‐infiltrating immune cells (TIICs), specifically CD8+ T cells, in the tumour microenvironment (TME) are related to tumour immune responses and are potential predictors for immunotherapeutic and survival outcomes. Therefore, we established a new CD8+ T cell‐related genes prognostic index (CD8T‐RGPI) for evaluating immune responses and prognostic outcomes for HCC. Using the TCGA databases, we evaluated the RNA‐seq data of CD8+ T cell‐related genes with gene co‐expression network. Then, the CD8T‐RGPI model was built by combining univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The nomogram exhibited a good prediction ability for HCC patients' prognosis in either TCGA or ICGC databases. The CD8T‐RGPI was elevated in patients with high T, M and TNM stages. Functional enrichment analyses revealed that in CD8T‐RGPI high‐risk group, tumour‐related and immunosuppressive pathways, such as focal adhesion, aerobic glycolysis, HIF1 transcription factor pathway, IL‐4 and IL‐13 signalling were significantly enriched. Moreover, for CD8T‐RGPI high‐risk HCC patients, immune tolerance and immunosurveillance escape was associated with poor therapeutic outcomes for ICB therapy. The CD8T‐RGPI low‐risk HCC patients with elevated immune infiltration levels were associated with good immunotherapeutic responses to ICB. Our findings provide prospective prognostic biomarkers and elucidate on HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the most common human malignancies worldwide and remains a major clinical challenge. Here, we found that benproperine phosphate (BPP), a cough suppressant, showed a significant anticancer effect on PC both in vitro and in vivo via the induction of autophagy‐mediated cell death. Mechanistic studies revealed that BPP triggered AMPK/mTOR‐mediated autophagy initiation and disturbed Ras‐related protein Rab‐11A (RAB11A)‐mediated autophagosome–lysosome fusion, resulting in excessive accumulation of autophagosomes. Inhibition of autophagy or overexpression of RAB11A partially reversed BPP‐induced growth inhibition in PC cells, suggesting that BPP might induce lethal autophagy arrest in PC cells. In conclusion, our results identify BPP as a potent antitumor agent for PC via the induction of autophagy arrest, therefore providing a new potential therapeutic strategy for the treatment of PC. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) could induce epithelial-mesenchymal transition (EMT) in residual tumours, resulting in rapid and aggressive recurrence. However, the role of EMT-related Long noncoding RNAs (lncRNAs) in residual tumour progression remains unclear. Methods: Insufficient RFA was simulated in vitro by heating Huh7 cells in water bath at 47 °C, named as Huh7-H. Cell invasion, migration assays and wound healing assay were conducted for functional analysis. Cell proliferation was determined by CCK8 assay. Differential expression profile of EMT-related lncRNAs between Huh7-H and Huh7 was analysed by LncPath human EMT array, and validated by qRT-PCR. Gain/loss-of-function assays of selected lncRNA were conducted by over-expressing or silencing its expression. Results: Huh7-H presented characteristic EMT morphological changes. WB analysis showed significantly decreased E-cadherin in Huh7-H cells. Transwell assays indicated the abilities of Huh7-H cells in migration and invasion were evidently strengthened. A new lncRNA, FUNDC2P4, was identified by LncPath human EMT array to be significantly down-regulated in Huh7-H cells. In vitro studies showed overexpression of FUNDC2P4 inhibited proliferation, invasion and migration potential and up-regulated E-cadherin expression in SMMC-7721 cells, whereas silencing FUNDC2P4 promoted these potentials and down-regulated E-cadherin expression in Huh7 cells. Conclusions: We explored that lncRNA FUNDC2P4 down-regulation promoted EMT leading to tumour proliferation, invasion and migration by reducing E-cadherin expression in residual HCC after insufficient RFA in vitro. These results suggest that FUNDC2P4 may have potentially therapeutic value for prevention and treatment of HCC recurrence after RFA in the future. [ABSTRACT FROM AUTHOR]

Purpose: Mixed formulation of fosrolapitant and palonosetron (PALO), HR20013, is a novel fixed-dose intravenous antiemetic combination that could simultaneously antagonize neurokinin-1 and 5-hydroxytryptamine-3 receptors. This study was designed to evaluate the efficacy and safety of HR20013 plus dexamethasone (DEX) versus fosaprepitant (FAPR) plus PALO + DEX for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC)., Methods: This is a noninferiority study. Chemotherapy-naïve patients were randomly assigned 1:1 to receive HR20013 (day 1) or FAPR + PALO (day 1) before each cycle of cisplatin-based HEC (two cycles in total), together with oral DEX (day 1-4). The primary end point was overall (0-120 hours) complete response (CR; no vomiting/no rescue therapy) rate in cycle 1. The key secondary end point was CR rate at the beyond delayed phase (120-168 hours) in cycle 1., Results: Three hundred seventy-three patients were enrolled to receive HR20013 + DEX and 377 to FAPR + PALO + DEX. The overall CR rate in cycle 1 was 77.7% for HR20013 + DEX and 78.2% for FAPR + PALO + DEX (difference = -0.9% [95% CI, -6.7 to 5.0]; one-sided P < .01), demonstrating that HR20013 + DEX was noninferior to FAPR + PALO + DEX. The superiority of HR20013 + DEX over FAPR + PALO + DEX in CR rate at the beyond delayed phase in cycle 1 was not met (90.3% v 86.5%; two-sided P = .11). In cycle 2, HR20013 + DEX showed greater proportions of patients reporting no impact on daily life at the delayed (24-120 hours) and beyond delayed phases compared with FAPR + PALO + DEX. The incidences of treatment-related adverse events were 35.7% during cycle 1 and 42.1% during entire study for HR20013 + DEX, versus 38.2% and 44.0% for FAPR + PALO + DEX., Conclusion: HR20013 + DEX was noninferior to FAPR + PALO + DEX for preventing HEC-CINV and well tolerated, with the potential to reduce the impact of CINV on daily life.