indocyanine-green-guided-intraoperative-imaging-to-facilitate-video

Indocyanine Green-Guided Intraoperative Imaging to Facilitate Video-Assisted Retroperitoneal Debridement for Treating Acute Necrotizing Pancreatitis

Video-assisted retroperitoneal debridement (VARD) is a feasible, minimally invasive necrosectomy method for treating severe acute necrotizing ...

Sun Yat-sen University

Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated β-catenin at Ser675, blocked β-catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-β-catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing β-catenin/ID2 activation, and was an independent prognostic factor in PDAC.

EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through β-catenin/ID2 pathway.

Long non-coding RNAs (lncRNAs) are emerging as important regulators and prognostic markers of multiple cancers. Our aim was to determine functional involvement of lncRNAs in pancreatic ductal adenocarcinoma (PDAC). In this study, we report that LINC01133 expression is higher in PDAC tissues compared to adjacent non-cancerous tissues, and this overexpression is associated with poorer prognosis among the patients. In vitro, a knockdown of LINC01133 substantially decreased PDAC cell proliferation. Tumorigenicity of PDAC cells with the LINC01133 knockdown was significantly impaired in a xenograft model assay. Moreover, we determined that CCAAT/enhancer-binding protein β (C/EBPβ) positively regulates LINC01133 expression by binding to the response elements within the LINC01133 promoter. Higher expression of C/EBPβ was observed in PDAC tissues, and this overexpression was also associated with the poorer prognosis. Furthermore, the LINC01133 knockdown decreased cyclin G1 (CCNG1) expression. Overexpression of CCNG1 attenuated the LINC01133 silencing-induced impairment of proliferation in PDAC cells. In summary, our findings revealed that the C/EBPβ-LINC01133 axis performs an oncogenic function in PDAC by activating CCNG1, which may serve as a prognostic biomarker or a therapeutic target in PDAC.

The C/EBPβ-LINC01133 axis promotes cell proliferation in pancreatic ductal adenocarcinoma through upregulation of CCNG1.

Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD) is a major complication that adversely affects recovery. The robotic approach may decrease the incidence of this complication. This propensity-matched analysis evaluates the impact of robotic PD (RPD) on CR-POPF.

Robotic Pancreaticoduodenectomy Is Associated with Decreased Clinically Relevant Pancreatic Fistulas: a Propensity-Matched Analysis.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the fourth leading cause of cancer-related death worldwide. Our previous study showed that EYA4 functioned by suppressing growth of HCC tumor cells, but its molecular mechanism is still not elucidated. Based on the results of gene microassay, EYA4 was inversely correlated with MYCBP and was verified in human HCC tissues by immunohistochemistry and western blot. Overexpressed and KO EYA4 in human HCC cell lines confirmed the negative correlation between EYA4 and MYCBP by qRT-PCR and western blot. Transfected siRNA of MYCBP in EYA4 overexpressed cells and overexpressed MYCBP in EYA4 KO cells could efficiently rescue the proliferation and G2/M arrest effects of EYA4 on HCC cells. Mechanistically, armed with serine/threonine-specific protein phosphatase activity, EYA4 reduced nuclear translocation of β-catenin by dephosphorylating β-catenin at Ser552, thereby suppressing the transcription of MYCBP which was induced by β-catenin/LEF1 binding to the promoter of MYCBP. Clinically, HCC patients with highly expressed EYA4 and poorly expressed MYCBP had significantly longer disease-free survival and overall survival than HCC patients with poorly expressed EYA4 and highly expressed MYCBP. In conclusion, EYA4 suppressed HCC tumor cell growth by repressing MYCBP by dephosphorylating β-catenin S552. EYA4 combined with MYCBP could be potential prognostic biomarkers in HCC.

EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β-catenin at Ser552.

In this study, we used bioinformatics tools to analyze transcriptome data from cholangiocarcinoma (CCA) patients in multiple datasets (Sun Yat-sen University, TCGA and GSE32225 cohorts) to identify mechanisms that regulate tumor infiltration by immune cells and survival outcomes. We identified 96 differentially expressed genes (DEGs), including 13 upregulated and 83 downregulated genes, in CCA tissues as regulatory T cells were significantly higher and the proportions of activated natural killer cells and monocytes were significantly lower in CCA tissues than the precancerous tissues. The survival outcomes of CCA patients were associated with the  gene mutation status, levels of Oncostatin M (OSM) expression, and the proportions of tumor-infiltrating immune cell types, including dendritic cells, monocytes, and T follicular helper cells. Functional enrichment analysis of the DEGs in the high OSM-expressing CCA tissues showed that pathways related to tumor progression and immune response were significantly upregulated. Our study demonstrates that OSM expression and  mutation status regulate the tumor infiltration by immune cells and survival outcomes in CCA. OSM is thus a potential prognostic biomarker and therapeutic target in cholangiocarcinoma.

Oncostatin M expression and  mutation status regulate tumor-infiltration of immune cells and survival outcomes in cholangiocarcinoma.

Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients.

Effect of bile duct resection on the prognosis of patients with hepatocellular carcinoma combined with extrahepatic bile duct tumor thrombus.

A novel approach to managing biliary anastomotic stricture following orthotopic liver transplantation after failure of endoscopic retrograde cholangiopancreatography technique.

Article	Year
EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through β-catenin/ID2 pathway. Cancer letters\| PubMed ID: 27378242	2016
The C/EBPβ-LINC01133 axis promotes cell proliferation in pancreatic ductal adenocarcinoma through upregulation of CCNG1. Cancer letters\| PubMed ID: 29458145	2018
Robotic Pancreaticoduodenectomy Is Associated with Decreased Clinically Relevant Pancreatic Fistulas: a Propensity-Matched Analysis. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract\| PubMed ID: 31267434	2019
EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β-catenin at Ser552. Cancer science\| PubMed ID: 31385398	2019
Oncostatin M expression and mutation status regulate tumor-infiltration of immune cells and survival outcomes in cholangiocarcinoma. Aging\| PubMed ID: 33216732	2020
Effect of bile duct resection on the prognosis of patients with hepatocellular carcinoma combined with extrahepatic bile duct tumor thrombus. BMC cancer\| PubMed ID: 39112950	2024
A novel approach to managing biliary anastomotic stricture following orthotopic liver transplantation after failure of endoscopic retrograde cholangiopancreatography technique. Endoscopy\| PubMed ID: 39809286	2025

Jianpeng Cai

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